We compared platelet aggregation and intracellular free calcium concentrations [( Ca2+]i) following stimulation with STA2, an analog of thromboxane A2 between patients with ischemic heart disease (IHD) showing significant stenosis in coronary angiograms and controls. In the presence of extracellular calcium, platelet aggregation and intracellular Ca2+ increase were enhanced by STA2 stimulation in a dose-dependent fashion and were higher in the IHD patients than in the controls. However, in the absence of extracellular calcium, no difference in intracellular Ca2+ increase was observed due to its total dependence on release from intracellular stores. These results suggest that thromboxane A2 increases platelet intracellular Ca2+-inducing aggregation, and this increase and aggregation, which is enhanced by thromboxane A2 in IHD patients, is due to promotion of Ca2+ influx by thromboxane A2. IHD patients appear to have an abnormality in the platelet membrane which may explain such thromboxane A2-dependent increased permeability to Ca2+.