Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology. It is characterized by platelet microthrombi in small vessels, which results in tissue dysfunction and a microangiopathic hemolytic anemia. Activation of coagulation is not a prominent feature of TTP. It is not known whether the process which results in platelet aggregate formation might also activate platelets. Using GMP-140 as a marker of activation, we examined the activation state of circulating platelets in seven TTP patients and three normal controls, as well as the ability of purified platelets from three TTP patients and three controls to be activated in vitro. There was no statistically significant difference in the percentage of activated platelets circulating in patients and controls (4% vs. 2%). Both TTP and control platelets increased GMP-140 expression and procoagulant activity after stimulation with thrombin or the calcium ionophore A23187. Thus, we conclude that TTP patients do not have a significantly increased proportion of circulating activated platelets, and their platelets can be activated normally by thrombin or a calcium ionophore.