Gross and microscopic findings consistent with acute (three patients) and healed (four patients) myocardial infarction were found in seven (9.7%) of 72 consecutive hearts from patients with sickle cell disease studied after autopsy between 1950 and 1982. Gross obstructive and atherosclerotic lesions were absent in all seven patients, while microthrombi were present in the arterioles of infarcted tissue in two patients. Pathophysiological mechanisms responsible for the infarction are unclear, but anemia, platelet thrombi, coronary vasospasm, and abnormal rheology related to sickle cells may all be important. Chest pain occurred clinically in six of the seven patients and ECG findings typical of infarction were found in two patients. One patient died suddenly. These findings suggest that ischemic heart disease may be present in a significant number of patients with sickle cell disease and should be considered in all patients who complain of chest pain, whether or not the patient is in crisis.