The very first presentation of ischemic heart disease-acute infarction, sudden death, or unstable angina-most often occurs abruptly. The first approximation that it occurs as a random event only when a certain "threshold severity" of coronary atherosclerosis has gradually developed, although widely accepted, should perhaps be reconsidered and expanded on the basis of the following considerations. Acute coronary occlusion leading to myocardial infarction often occurs at the site of mild or noncritical coronary stenoses. Conversely, in patients with chronic angina severe coronary stenoses can remain unchanged for years with no detectable progression. When a coronary artery occludes, the size of infarction can vary greatly, and when ischemia and infarction occur, malignant arrhythmias occur in some patients but not in others. Thus, in a second approximation, ischemic heart disease should be considered as the result of the variable combination of three major components: a) A very variable chronic atherosclerotic background, which can result from a variety of pathologic processes; b) A number of acute ischemic stimuli, which can unpredictably impair myocardial blood flow as a result of coronary thrombosis and/or vasoconstriction; c) A variable response of the heart to a sudden reduction of coronary blood flow in terms of collateral perfusion and malignant arrhythmias. Therefore, at one extreme end of the spectrum in any individual, ischemic syndromes may present predominantly as a result of an extremely large chronic background component. At the other extreme, powerful acute ischemic stimuli can unexpectedly impair blood supply by coronary thrombosis, constriction, or their combination, in the presence of a mild chronic atherosclerotic background. A fatal outcome can result from an arrhythmia caused by acute myocardial ischemia, which might have been transient or which might have caused a small infarction. The consideration of the separate pathogenetic and etiologic causes of these three components should set the stage for more understanding of the causes of ischemic syndromes, their rational management, and specific prevention.