The C-terminal dodecapeptide from human fibrinogen γ-chain, residues 400- 411, HHLG-GAKQAGDV (γ12), is known to inhibit fibrinogen-mediated platelet cell aggregation via competitive interactions with platelet glycoprotein integrin receptor GPIIb/IIIa. NMR studies of γ12 in the presence of purified GPIIb/IIIa (230 kDa) demonstrate that two γ12 binding states (γ12-I and γ12-II) are present on the integrin receptor. The N-terminal sequence HHLG is crucial to formation of γ12 state I since in a shorter γ-chain octapeptide, GAKQAGDV, γ12-I is not observed. Addition of the hexapeptide GRGDSP to the γ12-receptor preparation effectively removes the γ12-I population, suggesting either that γ12 and GRGDSP share one binding site or that their binding sites are allosterically linked. Distance geometry calculations using transfer NOEs from γ12-I (γ12-II shows practically no NOEs) indicate the presence of helix conformation when bound to the receptor. Line broadening and chemical shift changes relative to free γ12 suggest that γ12 interacts with GPIIb/IIIa primarily through N-terminal residues H400 to Q407.