AIM: To evaluate effects of diltiazem on platelet hyperreactivity in situations associated with endothelial injury and their possible relationship to cytosolic calcium concentration. METHODS: Blood samples were collected at 7 time points from 35 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) who received combined diltiazem and aspirin/ticlopidine therapy or aspirin/ticlopidine therapy alone. Platelet expression of glycoprotein Ⅱb/Ⅲa and cytosolic calcium concentration were measured, respectively, by whole blood flow cytometry and fluorospectrophotometry. The effects of diltiazem of different concentrations on expression of glycoprotein Ⅱb/Ⅲa were also studied in vitro in blood samples from patients with chronic stable angina. RESULTS: Of the two treatments, aspirin/ticlopidine therapy did not prevent an acute increase of expression of glycoprotein Ⅱb/Ⅲa 5 minutes and 10 minutes after first inflation and 10 minutes after PTCA, whereas combined diltiazem and aspirin/ticlopidine therapy had a significant inhibitory effect. In the group receiving aspirin/ticlopidine therapy, there was a short-term elevation of platelet [Ca~(2+)]i immediately following PTCA which was significantly reduced by diltiazem treatment. Expression of glycoprotein Ⅱb/Ⅲa was significantly inhibited in vitro by diltiazem in the concentration of 200 ?g/L or higher, but not 50 ?g/L. CONCLUSIONS: Combined diltiazem and aspirin/ticlopidine therapy significantly inhibited platelet activation that continued in the presence of conventional aspirin/ticlopidine treatment. Antiplatelet effects of diltiazem were probably a consequence of reduction of platelet [Ca~(2+)]i and may only be achieved in higher than therapeutic concentrations. [