Accurate assessment of the effects and mechanisms of action of any intervention altering exercise performance of patients with angina pectoris caused by coronary artery disease requires use of a carefully designed exercise protocol. Using such a protocol, we found that conditions tending to precipitate ischemic pain (meals, exposure to cold) usually are associated with circulatory changes that may increase myocardial oxygen consumption. Interventions causing symptomatic improvement (nitroglycerin, isosorbide dinitrate, beta blockade, physical training, and carotid sinus nerve stimulation) produce opposing effects. In addition to these studies, we review the evidence suggesting that angina or myocardial infarction may occur in patients with normal coronary arteries. Finally, we present an overall approach to the medical and operative treatment of patients with coronary artery disease.