To investigate the interaction between serotonin (5HT)(2) and α(2)-adrenergic receptors in the human platelet membrane, the inhibitory effects of calcium (Ca) antagonists, 5HT(2) antagonists, α(2) antagonists and adenosine (AE) receptor (A(2)) agonists on 5HT plus ADP ([5HT＋ADP]) and adrenaline (ADR) plus ADP ([ADR＋ADP])-induced washed platelet aggregation were examined. In the [5HT＋ADP] -induced aggregation. The inhibitory activity was in the order of (－)-desmethoxyverapamil (D888), mianserin (MA), ketanserin, AE>diltiazem, nicardipine, yohimbine. On the other hand, in the [ADR＋ADP] -induced aggregation, the inhibitory activity was in the order of MA, YH>D888, AE, and the rest had no significant effect even at 10 μM. Only AE among these drugs inhibited ADP-induced aggregation. The present findings indicate that the Ca antagonist D888, 5HT(2) antagonist MA and α(2) antagonist YH acted simultaneously as 5HT(2) and α(2) receptor inhibitors and imply an apparent interaction between these receptors. Since both of the aggregation responses required extracellular Ca(2+) and were modulated by Ca(2+) concentrations, the mechanism of interaction may be attributed to intracellular Ca(2+)-signaling systems.