The effects of 3 days of oral diltiazem, "low dose" aspirin (40 mg/day), and their combination on platelet function was studied in 5 normal subjects. Both drugs inhibited platelet aggregation and ATP release induced by collagen, epinephrine and threshold concentrations of ADP. Aspirin and diltiazem decreased thromboxane A2 generation during ADP induced aggregation by 94 percent and 53 percent respectively, however both agents inhibited aggregation similarly, which suggests that diltiazem's anti-platelet effect was due to mechanisms other than inhibition of thromboxane metabolism alone. Combination therapy resulted in a partially additive inhibitory effect on ADP induced aggregation and thromboxane A2 generation. Two subjects had bleeding times over 15 minutes after receiving combination therapy.