1
      AS FILED WITH THE SECURITIES AND EXCHANGE COMMISSION ON JULY 14, 2000
                                                    REGISTRATION NO. 333-
================================================================================

                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                             ----------------------

                                    FORM S-8
                             REGISTRATION STATEMENT
                                      UNDER
                           THE SECURITIES ACT OF 1933

                          LEXICON GENETICS INCORPORATED
             (EXACT NAME OF REGISTRANT AS SPECIFIED IN ITS CHARTER)

                                                                                 
                           DELAWARE                                                      76-0474169
                (STATE OR OTHER JURISDICTION OF                                       (I.R.S. EMPLOYER
                INCORPORATION OR ORGANIZATION)                                      IDENTIFICATION NO.)

                  4000 RESEARCH FOREST DRIVE
                     THE WOODLANDS, TEXAS                                                  77381
           (ADDRESS OF PRINCIPAL EXECUTIVE OFFICES)                                      (ZIP CODE)

                             ----------------------

                         2000 EQUITY INCENTIVE PLAN AND
                 2000 NON-EMPLOYEE DIRECTORS' STOCK OPTION PLAN
                           (FULL TITLES OF THE PLANS)

                             ----------------------

                          ARTHUR T. SANDS, M.D., PH.D.
                      PRESIDENT AND CHIEF EXECUTIVE OFFICER
                           4000 RESEARCH FOREST DRIVE
                           THE WOODLANDS, TEXAS 77381
                     (NAME AND ADDRESS OF AGENT FOR SERVICE)

                                 (281) 364-0100
          (TELEPHONE NUMBER, INCLUDING AREA CODE, OF AGENT FOR SERVICE)

                             ----------------------

                                   COPIES TO:

                 JEFFREY R. HARDER                                     JEFFREY L. WADE
               ANDREWS & KURTH L.L.P.                    EXECUTIVE VICE PRESIDENT AND GENERAL COUNSEL
          2170 BUCKTHORNE PLACE, SUITE 150                      LEXICON GENETICS INCORPORATED
             THE WOODLANDS, TEXAS 77380                           4000 RESEARCH FOREST DRIVE
                   (713) 220-4801                                 THE WOODLANDS, TEXAS 77381
                                                                        (281) 364-0100

                             ----------------------

                         CALCULATION OF REGISTRATION FEE

==================================================================================================================================
                                                                               PROPOSED
                                                                                MAXIMUM           PROPOSED
                                                           AMOUNT TO           OFFERING           MAXIMUM
  TITLE OF SECURITIES TO BE                              BE REGISTERED           PRICE           AGGREGATE           AMOUNT OF
         REGISTERED                TITLE OF PLAN              (1)            PER SHARE(2)     OFFERING PRICE(2)   REGISTRATION FEE
- ----------------------------------------------------------------------------------------------------------------------------------
                                                                                                  
Common Stock, par value
$0.001 per share ("Common     2000 Equity Incentive    11,250,000 shares       $ 41.50         $ 466,875,000         $ 123,288
Stock")                       Plan
- ----------------------------------------------------------------------------------------------------------------------------------
                              2000 Non-Employee
Common Stock                  Directors' Stock            600,000 shares       $ 41.50         $  24,900,000         $   6,600
                              Option Plan
==================================================================================================================================

 (1)     Pursuant to Rule 416(a), this registration statement shall cover any
         additional securities issued to prevent dilution resulting from stock
         splits, stock dividends or similar transactions.
(2)      Estimated solely for the purpose of calculating the registration fee
         pursuant to Rule 457 (c) and (h), based on the average of the high and
         low sales price per share of the Registrant's common stock, as reported
         on The Nasdaq National Market on July 13, 2000.

================================================================================

   2
                                     PART II

               INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

ITEM 3.  INCORPORATION OF DOCUMENTS BY REFERENCE.

         The following documents filed with the Securities and Exchange
Commission (the "Commission") by the Registrant are incorporated by reference in
this Registration Statement:

         (a)      The Registrant's prospectus filed pursuant to Rule 424(b)
                  under the Securities Act of 1933, as amended (the "Securities
                  Act"), on April 7, 2000, in connection with the Registration
                  Statement on Form S-1, as amended (No. 333-96469), originally
                  filed on February 9, 2000;

         (b)      The Registrant's Quarterly Report on Form 10-Q for the quarter
                  ended March 31, 2000; and

         (c)      The description of the common stock, par value $0.001 per
                  share (the "Common Stock"), of the Registrant contained in the
                  Registrant's Registration Statement on Form 8-A filed with the
                  Commission on March 27, 2000 pursuant to Section 12 of the
                  Securities Exchange Act of 1934, as amended (the "Exchange
                  Act"), including any amendments and reports filed for the
                  purpose of updating such description.

         All documents subsequently filed by the Registrant pursuant to Sections
13(a), 13(c), 14 and 15(d) of the Exchange Act, prior to the filing of a
post-effective amendment which indicates that all shares of Common Stock offered
hereby have been sold or which deregisters all shares of Common Stock then
remaining unsold, shall be deemed to be incorporated by reference herein and to
be part hereof from the date of the filing of such documents. Any statement
contained in a document incorporated or deemed to be incorporated by reference
herein shall be deemed to be modified or superseded for purposes of this
Registration Statement to the extent that a statement contained herein or in any
other subsequently filed document which also is or is deemed to be incorporated
by reference herein modifies or supersedes such statement. Any statement so
modified or superseded shall not be deemed, except as so modified or superseded,
to constitute a part of this Registration Statement.

ITEM 4.  DESCRIPTION OF SECURITIES.

         The information required by Item 4 is not applicable to this
registration statement because the class of securities to be offered is
registered under Section 12 of the Exchange Act.

ITEM 5.  INTERESTS OF NAMED EXPERTS AND COUNSEL.

         The information required by Item 5 is not applicable to this
registration statement.

ITEM 6.  INDEMNIFICATION OF DIRECTORS AND OFFICERS.

         Section 145 of the Delaware General Corporation Law ("DGCL") provides
that a corporation may indemnify any person who was or is a party or is
threatened to be made a party to any threatened, pending or completed action,
suit or proceeding whether civil, criminal, administrative or investigative
(other than an action by or in the right of the corporation by reason of the
fact that he is or was a director, officer, employee or agent of the
corporation, or is or was serving at the request of the corporation as a
director, officer, employee or agent of another corporation, partnership, joint
venture, trust or other enterprise, against expenses (including attorneys'
fees), judgments, fines and amounts paid in settlement actually and reasonably
incurred by him in connection with such action, suit or proceeding if he acted
in good faith and in a manner he reasonably believed to be in or not opposed to
the best interests of the corporation, and, with respect to any criminal action
or proceeding, had no reasonable cause to believe his conduct was unlawful.
Section 145 further provides that a corporation similarly may indemnify any such
person serving in any such capacity who was or is a party or is threatened to be
made a party to any threatened, pending or completed action or suit by or in the
right of the corporation to procure a judgment in its favor by reason of the
fact that he is or was a director, officer, employee or agent of the corporation
or is or was serving at the request of the corporation as a director, officer,
employee or agent of

                                      II-1
   3

another corporation, partnership, joint venture, trust or other enterprise,
against expenses (including attorneys' fees) actually and reasonably incurred in
connection with the defense or settlement of such action or suit if he acted in
good faith and in a manner he reasonably believed to be in or not opposed to the
best interests of the corporation and except that no indemnification shall be
made in respect of any claim, issue or matter as to which such person shall have
been adjudged to be liable to the corporation unless and only to the extent that
the Delaware Court of Chancery or such other court in which such action or suit
was brought shall determine upon application that, despite the adjudication of
liability but in view of all of the circumstances of the case, such person is
fairly and reasonably entitled to indemnity for such expenses which the Delaware
Court of Chancery or such other court shall deem proper.

         The Registrant's certificate of incorporation and bylaws provide that
indemnification shall be to the fullest extent permitted by the DGCL for all
current or former directors or officers. As permitted by the DGCL, the
certificate of incorporation provides that directors of the Registrant shall
have no personal liability to the Registrant or its stockholders for monetary
damages for breach of fiduciary duty as a director, except (1) for any breach of
the director's duty of loyalty to the Registrant or its stockholders, (2) for
acts or omissions not in good faith or which involve intentional misconduct or
knowing violation of law, (3) under Section 174 of the DGCL or (4) for any
transaction from which a director derived an improper personal benefit.

         The Registrant has entered into indemnification agreements with each of
its officers and directors. Each such agreement provides that each party to the
agreement shall have no personal liability to the Registrant or its stockholders
for monetary damages for breach of fiduciary duty as a director, except (1) for
any breach of the director's duty of loyalty to the Registrant or its
stockholders, (2) for acts or omissions not in good faith or which involve
intentional misconduct or knowing violation of law, (3) under Section 174 of the
DGCL or (4) for any transaction from which a director derived an improper
personal benefit. Each such agreement also provides an indemnification to each
party to the agreement against damages and expenses arising from claims against
such party for a breach of such party's fiduciary duty to the Registrant or its
stockholders.

ITEM 7.  EXEMPTION FROM REGISTRATION CLAIMED.

         The information required by Item 7 is not applicable to this
registration statement.

ITEM 8.  EXHIBITS.

   EXHIBIT
   NUMBER                              DESCRIPTION
   ------                              -----------

     4.1+        Restated Certificate of Incorporation (incorporated by
                 reference to Exhibit 3.1 to the Registrant's Registration
                 Statement on Form S-1 (No. 333-96469), originally filed on
                 February 9, 2000 (the "Registration Statement")).

     4.2+        Restated Bylaws (incorporated by reference to Exhibit 3.2 to
                 the Registration Statement).

     5.1*        Opinion of Andrews & Kurth L.L.P.

    23.1*        Consent of Andrews & Kurth L.L.P. (included in Exhibit 5.1).

    23.2*        Consent of Arthur Andersen LLP

    24.1*        Power of Attorney (set forth on the signature page contained in
                 Part II of this Registration Statement).

    99.1+        Lexicon Genetics Incorporated 2000 Equity Incentive Plan
                 (incorporated by reference to Exhibit 10.7 to the Registration
                 Statement).

                                      II-2
   4
      99.2+      Lexicon Genetics Incorporated Non-Employee Directors' Stock
                 Option Plan (incorporated by reference to Exhibit 10.8 to the
                 Registration Statement).
- --------------------------
+ Incorporated herein by reference.

* Filed herewith.

ITEM 9.  UNDERTAKINGS.

         (a)      The undersigned Registrant hereby undertakes:

                  (1) To file, during any period in which offers or sales are
         being made, a post-effective amendment to this registration statement:

                           (i) To include any prospectus required by Section
                  10(a)(3) of the Securities Act;

                           (ii) To reflect in the prospectus any facts or events
                  arising after the effective date of this registration
                  statement (or the most recent post-effective amendment
                  thereof) which, individually or in the aggregate, represent a
                  fundamental change in the information set forth in this
                  registration statement;

                           (iii) To include any material information with
                  respect to the plan of distribution not previously disclosed
                  in this registration statement or any material change to such
                  information in this registration statement;

         Provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) above do
         not apply if the information required to be included in a
         post-effective amendment by those paragraphs is contained in periodic
         reports filed by the Registrant pursuant to Section 13 or Section 15(d)
         of the Exchange Act that are incorporated by reference in the
         registration statement.

                  (2) That, for the purpose of determining any liability under
         the Securities Act, each such post-effective amendment shall be deemed
         to be a new registration statement relating to the securities offered
         therein, and the offering of such securities at that time shall be
         deemed to be the initial bona fide offering thereof.

                  (3) To remove from registration by means of a post-effective
         amendment any of the securities being registered which remain unsold at
         the termination of the offering.

         (b) The undersigned Registrant hereby undertakes that, for purposes of
determining any liability under the Exchange Act, each filing of the
Registrant's annual report pursuant to Section 13(a) or 15(d) of the Exchange
Act that is incorporated by reference in this Registration Statement shall be
deemed to be a new registration statement relating to the securities offered
therein, and the offering of such securities at that time shall be deemed to be
the initial bona fide offering thereof.

         (c) Insofar as indemnification for liabilities arising under the
Securities Act may be permitted to directors, officers and controlling persons
of the Registrant pursuant to the foregoing provisions, or otherwise, the
Registrant has been advised that in the opinion of the Commission such
indemnification is against public policy as expressed in the Securities Act and
is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the Registrant of expenses
incurred or paid by a director, officer or controlling person of the Registrant
in the successful defense of any action, suit or proceeding) is asserted by such
director, officer or controlling person in connection with the securities being
registered, the Registrant will, unless in the opinion of its counsel the matter
has been settled by controlling precedent, submit to a court of appropriate
jurisdiction the question whether such indemnification by it is against public
policy as expressed in the Securities Act and will be governed by the final
adjudication of such issue.

                                      II-3
   5
                                   SIGNATURES

         Pursuant to the requirements of the Securities Act of 1933, as amended,
the Registrant has duly caused this registration statement to be signed on its
behalf by the undersigned, thereunto duly authorized, in The Woodlands, in the
State of Texas, on July 14, 2000.

                                       LEXICON GENETICS INCORPORATED

                                       By: /s/  ARTHUR T. SANDS, M.D., PH.D.
                                           ---------------------------------
                                                Arthur T. Sands, M.D., Ph.D.,
                                           President and Chief Executive Officer

                                POWER OF ATTORNEY

         The person whose signature appears below appoints Arthur T. Sands,
M.D., Ph.D., Julia P. Gregory and Jeffrey L. Wade, and each of them, any of whom
may act without the joinder of the other, as his true and lawful
attorneys-in-fact and agents with full power of substitution and resubstitution,
for him and in his name, place and stead, in any and all capacities, to sign any
and all amendments (including post-effective amendments) to this Registration
Statement and any Registration Statement (including any amendment thereto) for
this offering that is to be effective upon filing pursuant to Rule 462(b) under
the Securities Act of 1933, as amended, and to file the same, with all exhibits
thereto, and all other documents in connection therewith, with the Securities
and Exchange Commission, granting unto said attorneys-in-fact and agents full
power and authority to do and perform each and every act and thing requisite and
necessary to be done, as fully to all intents and purposes as he might or would
do in person, hereby ratifying and confirming all that said attorneys-in-fact
and agents or any of them or their or his substitute and substitutes, may
lawfully do or cause to be done by virtue hereof.

         PURSUANT TO THE REQUIREMENTS OF THE SECURITIES ACT OF 1933, AS AMENDED,
THIS REGISTRATION STATEMENT HAS BEEN SIGNED BELOW BY THE FOLLOWING PERSONS IN
THE CAPACITIES AND ON THE DATES INDICATED BELOW.

                       SIGNATURE                                      TITLE                          DATE
                       ---------                                      -----                          ----
                                                                                               
           /s/ ARTHUR T. SANDS, M.D., PH.D.                 President, Chief Executive          July 14, 2000
           --------------------------------                    Officer and Director
             Arthur T. Sands, M.D., Ph.D.                 (principal executive officer)

                 /s/ JULIA P. GREGORY                      Executive Vice President and         July 14, 2000
                 --------------------                        Chief Financial Officer
                   Julia P. Gregory                          (principal financial and
                                                               accounting officer)

                /s/ THOMAS CASKEY, M.D.                      Chairman of the Board of           July 14, 2000
                -----------------------                             Directors
                  Thomas Caskey, M.D.

                 /s/ STEPHEN J. BANKS                                Director                   July 14, 2000
                 --------------------
                   Stephen J. Banks

                                      II-4
   6

                                                                                          
               /s/ SAM L. BARKER, Ph.D.                              Director                   July 14, 2000
               ------------------------
                 Sam L. Barker, Ph.D.

                  /s/ GORDON A. CAIN                                 Director                   July 14, 2000
                  ------------------
                    Gordon A. Cain

               /s/ PATRICIA M. CLOHERTY                              Director                   July 14, 2000
               ------------------------
                 Patricia M. Cloherty

               /                    /                                Director                   July 14, 2000
               ---------------------
                  Paul Haycock, M.D.

                 /s/ WILLIAM A. McMINN                               Director                   July 14, 2000
                 ---------------------
                   William A. McMinn

                                      II-5
   7
                                  EXHIBIT INDEX

EXHIBIT
NUMBER                               DESCRIPTION
- ------                               -----------

     4.1+        Restated Certificate of Incorporation (incorporated by
                 reference to Exhibit 3.1 to the Registrant's Registration
                 Statement on Form S-1 (No. 333-96469), originally filed on
                 February 9, 2000 (the "Registration Statement")).

     4.2+        Restated Bylaws (incorporated by reference to Exhibit 3.2 to
                 the Registration Statement).

     5.1*        Opinion of Andrews & Kurth L.L.P.

    23.1*        Consent of Andrews & Kurth L.L.P. (included in Exhibit 5.1).

    23.2*        Consent of Arthur Andersen LLP

    24.1*        Power of Attorney (set forth on the signature page contained in
                 Part II of this Registration Statement).

    99.1+        Lexicon Genetics Incorporated 2000 Equity Incentive Plan
                 (incorporated by reference to Exhibit 10.7 to the Registration
                 Statement).

    99.2+        Lexicon Genetics Incorporated Non-Employee Directors' Stock
                 Option Plan (incorporated by reference to Exhibit 10.8 to the
                 Registration Statement).
- ----------------------------

+ Incorporated herein by reference.
* Filed herewith.

   1
                                                                     EXHIBIT 5.1

                                  July 14, 2000

Board of Directors
Lexicon Genetics Incorporated
4000 Research Forest Drive
The Woodlands, Texas 77381

Ladies and Gentlemen:

         We have acted as counsel to Lexicon Genetics Incorporated (the
"Company") in connection with the Company's Registration Statement on Form S-8
(the "Registration Statement") relating to the registration under the Securities
Act of 1933, as amended, of the issuance of up to (i) 11,250,000 shares (the
"Equity Incentive Plan Shares") of the Company's common stock, par value $0.001
per share (the "Common Stock"), pursuant to the Company's 2000 Equity Incentive
Plan (the "Equity Incentive Plan"); and (ii) 600,000 shares (the "Director Plan
Shares" and, together with the Equity Incentive Plan Shares, the "Shares") of
Common Stock, pursuant to the Company's 2000 Non-Employee Directors' Stock
Option Plan (the "Director Plan" and, together with the Equity Incentive Plan,
the "Plans").

         In connection herewith, we have examined copies of such statutes,
regulations, corporate records and documents, certificates of public and
corporate officials and other agreements, contracts, documents and instruments
as we have deemed necessary as a basis for the opinion hereafter expressed. In
such examination, we have assumed the genuineness of all signatures, the
authenticity of all documents submitted to us as originals and the conformity
with the original documents of all documents submitted to us as copies. We have
also relied, to the extent we deem such reliance proper, on information supplied
by officers and employees of the Company with respect to various factual matters
material to our opinion.

         Based on the foregoing and having due regard for such legal
considerations as we deem relevant, we are of the opinion that the Shares have
been duly authorized, and that such Shares will, when issued in accordance with
the terms of the Plans, be duly authorized, fully paid and validly issued.

         This opinion is limited in all respects to the General Corporation Law
of the State of Delaware and the laws of the United States of America insofar as
such laws are applicable.

         We hereby consent to the use of this opinion as an exhibit to the
Registration Statement. In giving this consent, we do not thereby admit that we
are within the category of persons whose consent is required under Section 7 of
the Securities Act or the rules and regulations of the Securities and Exchange
Commission thereunder.

                                                     Very truly yours,

                                                     ANDREWS & KURTH L.L.P.

   1
                                                                    EXHIBIT 23.2

                    CONSENT OF INDEPENDENT PUBLIC ACCOUNTANTS

         As independent public accountants, we hereby consent to the
incorporation by reference in this registration statement of our report dated
February 4, 2000 included in the Registration Statement on Form S-1 of Lexicon
Genetics Incorporated (No. 333-96469), originally filed with the Securities and
Exchange Commission on February 9, 2000, and to all references to our Firm
included in this registration statement.

ARTHUR ANDERSEN LLP

Houston, Texas
July 12, 2000