In order to compare binding of small peptide mimetics on activated vs resting platelets and with fibrinogen (fgn) on activated platelets, the binding of [3H]-SC-52012, a low molecular weight (483) mimetic of the RGDF sequence present in fgn, was evaluated. This compound is a potent inhibitor of fgn binding to activated platelets, IC, 9.0±0.6 nM (mean±SEM), and inhibits ADP induced human platelet aggregation (IC, 44±5 nM). The dissociation constant (Kd) of [3H]-SC-52012 was 21.6±4.7 nM (n = 13) in ADP-induced human washed platelets while the Kd for resting platelets was 156±8.3 nM (n = 3). The maximum number of binding sites on ADP-activated and resting platelets were 60846±7158 and 59464±5898 molecules/platelet, respectively. By comparison, results with [125I]-fgn binding to activated platelets gave values of 363±73 nM and 58046±6386 molecules/platelet (n = 8) for the Kd and receptor number, respectively. These data suggest that the small molecule binds regardless of activation state of the platelet with only a change in affinity. [3H]-SC-52012 could be displaced by unlabelled SC-52012 with an IC50of 135±20 nM.