Endorphins and endorphin receptors are believed to modulate pain perception. To investigate whether naloxone, a specific antagonist, could initiate anginal pain during exercise-induced myocardial ischemia in asymptomatic patients with angiographically defined coronary artery disease, a single-blind trial was conducted in 10 men with prior positive exercise electrocardiograms. Multistage treadmill exercise tests were performed twice within a week. On the second test, patients received naloxone, 2 mg intravenously, by a syringe infusion pump. Exercise was terminated because of fatigue in 6 patients and completion of the protocol in 4. No patient reported chest pain during exercise. Naloxone did not significantly alter exercise duration, heart rate, blood pressure and ST-segment changes compared with control testing. It is concluded that endorphins do not play a significant role in the recognition of anginal pain in patients who have asymptomatic exercise-induced ischemia.