The cause of death in patients who die suddenly or after an acute myocardial infarction is, in most cases, ventricular fibrillation. Most of these patients suffer from ischemic heart disease and atherosclerotic narrowing of the coronary arteries. Ischemic changes include hypoxia, accumulation of metabolites, depletion of energy-yielding substrates, ionic shifts and structural changes. There is an increased sympathetic activity and often a higher vagal tone. Recent observations support the idea that there is an elevated regional adrenergic activity in the ischemic area with increased tissue levels of cyclic AMP. This seems to be one of several important factors contributing to the occurrence of ventricular fibrillation. Increased sympathetic activity might mediate reentry mechanisms as well as enhanced automaticity.