An extensive histopathological study was carried out on the hearts of 108 patients with electrocardiographically proven acute myocardial infarction dying after admission to a coronary care unit. The occluded or the narrowest segments of the coronary arteries were examined at intervals of 100 mu using serial sections. Serial sectioning is important in such a study because the pathology of the lumen can vary considerably within a 2 to 3 mm segment. A high incidence (80.3%) of thrombus formation corresponding to the site of infarction was observed. These thrombi occluded the vessel lumen, were usually found proximally in the coronary arteries, and were associated with a ruptured atheromatous plaque in 90.8 per cent of cases. It is postulated that an increase of intraplaque pressure resulting from a honeycomb-like accumulation of foam cells, cholesterol clefts, and blood infiltration through the injured endothelial cells is the cause of rupture of the atheromatous plaque. This rupture into the vessel lumen may precede, and be responsible for, formation of thrombus and the onset of acute myocardial infarction.