Thirty-two patients with thrombocythemia associated with myeloproliferative syndromes were selected on the basis of normal bleeding time and absence of hemorrhagic or thrombotic history. Twenty-five control subjects were studied simultaneously. They were all given a single intravenous infusion of 500 mg of aspirin (lysine acetylsalicylate), and bleeding time was measured two hours later. Both in the control group and in the patient group, aspirin significantly prolonged the bleeding time, but the average prolongation was significantly more pronounced in the patients. In comparison with the control subjects, the patients had a statistically significant reduction of platelet serotonin content and no difference in the production of platelet lipoxygenase derivative 12-HETE or plasma von Willebrand factor properties. Fourteen patients had abnormal platelet aggregation in response to adenosine diphosphate, adrenaline (epinephrine), or collagen. In six of them, all with very low serotonin content, the bleeding time was prolonged above the upper limit of the post-aspirin values in the control group. Thus, cyclooxygenase inhibition by aspirin unmasked a bleeding tendency in patients with a severe reduction in platelet dense bodies content. These findings might be relevant in relation to the use of antiplatelet drugs.