Recent evidence suggests that a short-lived product of prostaglandin biosynthesis produced on the addition of arachidonic acid to platelet microsomes is involved in physiologic platelet aggregation and mediates the release reaction by producing the platelet contractile wave. An important corollary of this hypothesis is that aspirin and indomethacin, inhibitors of prostaglandin synthesis, should block the platelet contractile process produced by agents which can initiate platelet aggregation. The present study tested this hypothesis and found that aspirin and indomethacin were, indeed, potent inhibitors of the platelet contractile wave stimulated by collagen and epinephrine, but largely failed to inhibit internal transformation induced by thrombin and ADP. The findings confirm the hypothesis that a prostaglandin produced endogenously by platelets initiates platelet contraction and suggests that ADP and thrombin have the ability to stimulate the platelet contractile apparatus by an alternate mechanism not dependent on prostaglandin synthesis.