Summary lntegrin alI& (platelet GPllb-llla) binds fibrinogen via recognition sequences such as Arg-Gly-Asp (RGD). Fibrinogen binding requires agonist activation of platelets, whereas the binding of short synthetic RGD peptides does not. We now find that RGD peptide binding leads to changes in aI& that are associated with acquisition of high affinity fibrinogen-binding function (activation) and subsequent platelet aggregation. The structural specificities for peptide activation and for inhibition of ligand binding are similar, indicating that both are consequences of occupancy of the same site (s) on al&. Thus, the RGD sequence is a trigger of high affinity ligand binding to a,, &, and certain RGD-mimetics are partial agonists as well as competitive antagonists of integrin function.