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                                                                    EXHIBIT 5.01



                             HOGAN & HARTSON L.L.P.
                            111 South Calvert Street
                            Baltimore, Maryland 21202



                                November 17, 2000



Board of Directors
Guilford Pharmaceuticals Inc.
6611 Tributary Street
Baltimore, MD 21224

Ladies and Gentlemen:

         We are acting as counsel to Guilford Pharmaceuticals Inc., a Delaware
corporation (the "Company"), in connection with its registration statement on
Form S-3, as amended (the "Registration Statement") filed with the Securities
and Exchange Commission relating to the proposed public offering of up to
3,500,000 shares of the Company's common stock, par value $0.01 per share, all
of which shares (the "Shares") are to be sold by the Company. This opinion
letter is furnished to you at your request to enable you to fulfill the
requirements of Item 601(b)(5) of Regulation S-K, 17 C.F.R. Section
229.601(b)(5), in connection with the Registration Statement.

         For purposes of this opinion letter, we have examined copies of the
following documents:

                  1.       An executed copy of the Registration Statement.

                  2.       The Certificate of Incorporation of the Company, as
                           certified by the Secretary of the State of the State
                           of Delaware on November 15, 2000 and by the Secretary
                           of the Company on the date hereof as then being
                           complete, accurate and in effect.


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                  3.       The Bylaws of the Company, as certified by the
                           Secretary of the Company on the date hereof as then
                           being complete, accurate and in effect.

                  4.       Resolutions of the Board of Directors of the Company
                           adopted at a special meeting held on October 19,
                           2000, as certified by the Secretary of the Company on
                           the date hereof as being complete, accurate and in
                           effect, relating to the issuance and sale of the
                           Shares and arrangements in connection therewith.

         In our examination of the aforesaid documents, we have assumed the
genuineness of all signatures, the legal capacity of all natural persons, the
accuracy and completeness of all documents submitted to us, the authenticity of
all original documents, and the conformity to authentic original documents of
all documents submitted to us as copies (including telecopies). This opinion
letter is given, and all statements herein are made, in the context of the
foregoing.

         This opinion letter is based as to matters of law solely on Delaware
General Corporation Law, as amended. We express no opinion herein as to any
other laws, statutes, ordinances, rules, or regulations. As used herein, the
term "Delaware General Corporation Law, as amended" includes the statutory
provisions contained therein, all applicable provisions of the Delaware
Constitution and reported judicial decisions interpreting these laws.

         Based upon, subject to and limited by the foregoing, we are of the
opinion that following (i) effectiveness of the Registration Statement, (ii)
issuance of the Shares pursuant to the terms of any agreement therefor, and
(iii) receipt by the Company of the consideration for the Shares specified in
the resolutions of the Board of Directors or a properly constituted committee
thereof, the Shares will be validly issued, fully paid and nonassessable.

         This opinion letter has been prepared for your use in connection with
the filing of the Registration Statement and speaks as of the date hereof. We
assume no obligation to advise you of any changes in the foregoing subsequent to
the delivery of this opinion letter.



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         We hereby consent to the filing of this opinion letter as Exhibit 5.01
to the Registration Statement and to the reference to this firm under the
caption "Legal Matters" in the prospectus constituting a part of the
Registration Statement. In giving this consent, we do not thereby admit that we
are an "expert" within the meaning of the Securities Act of 1933, as amended.

                                                    Very truly yours,

                                                    /s/ HOGAN & HARTSON L.L.P.

                                                    HOGAN & HARTSON L.L.P.