1. The effects of suramin, a trypanocidal drug which has been reported to be a P2-purinoceptor antagonist on smooth muscle, were investigated in human platelets, where adenosine 5'-diphosphate (ADP) induces aggregation by acting on a subtype of purinoceptors which has been called P2T. 2. Suramin (100 microM) had no inhibitory effect on ADP-induced platelet aggregation in plasma, even after 40 min incubation in the presence of bacitracin, a peptidase inhibitor, and did not affect the ability of adenosine 5'-triphosphate (ATP) (40 microM) to inhibit competitively ADP-induced aggregation. This lack of effect of suramin on platelets in plasma is probably due to its extensive binding to plasma proteins. 3. In washed platelets, suramin (50-400 microM) acted as an apparently competitive antagonist, causing parallel shifts to the right of the log concentration-response curve to ADP. No depression of the maximal response to ADP was observed at concentrations of suramin (50-150 microM) for which full log concentration-response curves to ADP could be obtained, but the slope of the Schild plot was around 2, indicating that this antagonism was not simply competitive. The apparent pA2 value for suramin, taken from this Schild plot, was 4.6. 4. Suramin (200-400 microM) also noncompetitively inhibited aggregation induced by U46619 (a thromboxane receptor agonist) or by 5-hydroxytryptamine in the presence of adrenaline (100 microM), and caused a depression of the maximal response to these agonists. This nonspecific effect of suramin may explain the high Schild plot slope obtained against ADP.5. These results provide evidence that the ADP receptor on human platelets is indeed similar to the P2-purinoceptors responding to adenine nucleotides on smooth muscle and other tissues, and show that suramin cannot distinguish between the proposed subtypes of the P2-purinoceptors.