A pentadecapeptide, derived from a staphylococcal protease digest of the 27-residue carboxy-terminal cyanogen bromide fragment of human fibrinogen gamma chain, inhibits binding of 125I-fibrinogen to human platelet receptors and aggregation of platelets induced by ADP and fibrinogen. Amino acid composition and NH2 terminal analysis indicate that the isolated pentadecapeptide corresponds to residues 397 to 411 of the gamma chain. A synthetic peptide also inhibited binding of 125I-fibrinogen and aggregation of platelets. In contrast, the isolated pentadecapeptide and its parent 27-residue fragment lack inhibitory activity toward the polymerization reaction of fibrin monomer. Thus, the site recognizing the platelet receptor encompasses residues 397-411 of the gamma chain of fibrinogen and is distinct from the site(s) involved in polymerization of fibrin monomers.