This study assessed the effect of low (40 mg) and high (324 mg) single dose aspirin on cardiac release of thromboxane A2 and prostacyclin as assessed by measurement of coronary sinus levels of metabolites in patients with coronary artery disease. Measurements were done in the resting state and in the presence of pacing stress prior to and 24 h after aspirin administration. There was no consistent response in prostaglandin release under conditions of tachycardia stress as compared to control. Following both doses of aspirin, thromboxane could not be detected at rest or with pacing, and prostacyclin metabolic levels were undetectable in six of seven patients. Prostaglandin levels were not related to myocardial lactate extraction or production and lactate levels had no consistent relationship to aspirin administration. These data indicate that both low and high doses of aspirin inhibit both thromboxane A2 and prostacyclin production in humans. Selective thromboxane inhibition might not be possible.