A series of investigations on the determinants of myocardial oxygen consumption were reviewed and their relevance to the survival and function of ischemic tissue in the presence of coronary occlusion pointed out. Tension development, contractile state of the myocardium, and heart rate are the most important factors influencing cardiac oxygen consumption, and drugs commonly used in the treatment of patients with acute myocardial infarction appear to influence oxygen consumption by acting upon these three determinants. Thus, digitalis glycosides and sympathomimetic agents tend to increase myocardial oxygen requirements, since they improve the heart's inotropic state. However, this influence may be offset in the enlarged heart in which end-diastolic volume and tension are reduced. Agents which depress the heart exert the opposite effect. Electrocardiographic changes reflecting myocardial ischemia are intensified when isoproterenol is administered following coronary ligation. Synchronized arterial counterpulsation reduces myocardial tension development and therefore oxygen consumption. An augmentation of myocardial oxygen needs in the presence of coronary occlusion may be expected to increase the size of the necrotic zone and to impair the function of the ischemic zone, while a reduction of oxygen consumption may be expected to exert the opposite effect.