Aspirin and ticlopidine are used to prevent arterial thrombosis. In some clinical settings ticlopidine is administered with aspirin for improving antithrombotic effect. We adminis tered aspirin (100 mg/day), ticlopidine (500mg/day), or ticlo pidine and aspirin for 7 days to healthy volunteers. Platelet aggregation and ATP release induced by sodium arachidonate, ADP, or a combination of both were measured. Sodium ara chidonate (0.25 mmol/L), which produces no platelet aggrega tion, combined with adenosine diphosphate (1 μmol/L), which produced a reversible platelet aggregation of 20% after ticlo pidine, resulted in a synergistic platelet aggregation response in normal (74.6 ± 9.2%) and in ticlopidine platelet-rich plasma (59.1% ± 14.9%, p < 0.0001). Synergism after sodium arachi donate (0.75 mmol/L) plus adenosine diphosphate (4 μmol/L) fell from 75.8% ± 11.0% and 59.1% ± 15.6% after ticlopidine or aspirin, respectively, to 14.8% ± 18.0% (p < 0.0001) after ticlopidine plus aspirin. Aspirin and ticlopidine alone did not inhibit adenosine triphosphate release as thoroughly as did as pirin plus ticlopidine. Aspirin or ticlopidine does not ad equately prevent platelet activity as ticlopidine plus aspirin do. Addition of aspirin to treatment with ticlopidine improves their antiplatelet activity and better results could be obtained in ar terial thrombotic prevention strategies.