Because of recent findings, a reassessment is needed of the concept that rest angina associated with ST-segment depression is due to a spontaneous, transient increase of blood pressure or heart rate, or both, in the presence of critical coronary artery stenosis. Continuous hemodynamic and electrocardiographic recordings done before and during attacks of rest angina and thallium-201 scintigrams done during pain indicate that a transient reduction of flow is the immediate cause of ischemia in most, but not all, instances. Flow reduction, in turn, appears to be due to coronary arterial spasm or platelet aggregation, or both, acting at a site of atherosclerotic narrowing. Therapy for unstable rest angina should include measures to prevent both transient reductions of flow and increases of myocardial oxygen consumption. A combination of long-acting nitrates, a beta-blocker, a calcium-channel blocker, and aspirin or heparin is suggested for this purpose. Intravenous nitroglycerin is useful when angina occurs despite this therapy or when frequent attacks of ischemia are occurring at the time of admission.