Suspecting that platelet thromboemboli could play a role in the pathogenesis of myocardial ischemia, we have done a random-order, double-blind, crossover study of the effect of the platelet-active drug sulfinpyrazone on treadmill exercise-induced angina pectoris in 30 men with coronary artery disease. The mean duration of exercise before onset of angina was 43 s longer after taking sulfinpyrazone than before and 11s shorter after taking placebo than before. Analysis of variance for crossover design showed that the mean difference between the values obtained before and after sulfinpyrazone was significantly different (p < 0.01) from the mean difference between the values before and after placebo. Sulfinpyrazone had no effect on the mean heart rate-blood pressure product at onset of angina, change in ST segment during exercise, or preexercise platelet aggregate ratio and bleeding time. Exercise until angina occurred did not affect the platelet aggregate ratio.