AMENDMENT NO. 4 TO AMENDED AND

                         RESTATED STOCKHOLDERS AGREEMENT



          AMENDMENT NO. 4 dated and effective as of September 1, 2000, to

Amended and Restated Stockholders Agreement dated as of April 30, 1998 by and

among PRAECIS PHARMACEUTICALS INCORPORATED, a Delaware corporation (the

"Company"), and the Stockholders of the Company referred to therein, as amended

by Amendment No. 1 dated as of May 14, 1998, Amendment No. 2 dated as of July

21, 1998 and Amendment No. 3 dated as of January 31, 2000 (the "Stockholders

Agreement"). Capitalized terms used herein and not otherwise defined shall have

the meanings ascribed to such terms in the Stockholders Agreement.



          Article 8 of the Stockholders Agreement provides that upon the

consummation of an Initial Public Offering, the Stockholders Agreement will

terminate, except for certain specified provisions, including Article 6 which

provides for certain demand and piggyback registration rights and certain

obligations in connection therewith.



          The Company consummated an Initial Public Offering on May 2, 2000, and

the Company and the Stockholders who or which have executed this Amendment No. 4

desire to amend certain surviving provisions of the Stockholders Agreement as

provided herein.



          This Amendment No. 4 has been duly executed by the Company and by

Stockholders holding the requisite number of shares of Common Stock required by

Section 9.2 of the Stockholders Agreement.



          In consideration of the foregoing, the parties hereto, intending to be

legally bound, hereby agree as follows:



          1. AMENDMENT OF SECTION 6.1 (K). Section 6.1(k) of the Stockholders

Agreement is hereby amended in its entirety to read as follows:



          "(k) Notwithstanding the foregoing, in the event that the Company

               intends to commence a public offering of securities and the

               Board, with the concurrence of a majority of directors who are

               not employees of the Company, determines that a registration

               request under this Section 6.1 should be deferred, the Company

               shall so notify the holders of Registrable Securities in writing

               and such holders shall be deemed to have waived their rights to

               demand registration under this Section 6.1 for a period of 120

               days following such notice."







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          2. DELETION OF SECTION 6.3(C). Section 6.3(c) is hereby deleted in its

entirety, and, solely to preserve the correctness of prior numbering and

cross-references to other Sections of the Stockholders Agreement, the following

is inserted in lieu thereof:



          "(c) [Intentionally omitted]"



          3. AMENDMENT OF DEFINITION OF "REGISTRABLE SECURITIES". For all

purposes of the Stockholders Agreement, clause (ii) of the second sentence of

the definition of "Registrable Securities" shall be amended to read as follows:



          "(ii) they shall have been transferred pursuant to Rule 144 or are

               eligible to be transferred pursuant to Rule 144(k) or any

               successor provision,"



          4. AMENDMENT OF SECTION 8.1(C). Section 8.1(c) of the Stockholders

Agreement is hereby amended in its entirety to read as follows:



          "(c) The provisions set forth in Article 6, this Section 8.1(c) and

               Article 9 shall survive the termination of Agreement, provided,

               however, that at the close of business on September 1, 2000,

               Section 6.2, and all rights and obligations thereunder, shall

               automatically terminate and be of no further force or effect."



          5. AMENDMENT OF SECTION 9.1. Section 9.1 of the Stockholders Agreement

is hereby amended in its entirety to read as follows:



          "Section 9.1 SUCCESSORS AND ASSIGNS. The terms and provisions of this

Agreement, to the extent still in effect, shall be binding upon, and shall inure

solely to the benefit of and be enforceable solely by, the parties hereto

(including any nominee of a Stockholder which holds Common Stock in its name

which is beneficially owned by such Stockholder), except that the rights of a

Stockholder under Article 6 shall be assignable to an Affiliate of such

Stockholder to whom or which a Stockholder has transferred Registrable

Securities (if and for so long as such Affiliate continues to hold Registrable

Securities), provided the transferring Stockholder has notified the Company in

writing of such transfer and such Affiliate has agreed in writing with the

Company to be bound by this Agreement to the extent still in effect. Any breach

of any of the terms or provisions of this Agreement by a nominee of any

Stockholder shall be deemed a breach of this Agreement by such Stockholder."



          6. AMENDMENT OF SECTION 9.2. The first paragraph of Section 9.2 of the

Stockholders Agreement is hereby amended in its entirety to read as follows:





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               "(a) This Agreement may be amended only by a written instrument

duly executed by (i) the Company and (ii) Stockholders who own at least 66_% of

the Registrable Securities, provided that notwithstanding the foregoing, without

the prior consent or approval of the holders of a majority of the Registrable

Securities consisting of shares of Common Stock into which the shares of Series

E Preferred Stock were converted upon consummation of the Company's Initial

Public Offering (the holders of such Registrable Securities being referred to as

the "Series E Pre-IPO Preferred Stockholders"), this Agreement may not be

amended if such proposed amendment affects the rights under this Agreement (to

the extent still in effect) of the Series E Pre-IPO Preferred Stockholders who

hold Registrable Securities but does not so affect the rights of Stockholders

holding Registrable Securities consisting of shares of Common Stock into which

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