Using a quantitative, computer-aided circumferential profile technique, we have shown that thallium-201 scintigrams with large defects can identify a group of patients with a high mortality after acute myocardial infarction. To determine whether high-risk thallium scintigrams predict poor survival because of a critical loss of myocardium, we correlated infarct size in 24 autopsied patients with the extent of thallium defect in three views. Of 13 patients with large defects (computer score 7.0) eight (62%) had > 25% loss of left ventricular (LV) myocardium, but five (38%) had smaller infarcts (4-24% of LV myocardium), suggesting that part of the scintigraphic defect was related to ischemia without necrosis. Eight of nine patients with loss > 25% LV myocardium had large defects. In 10 of 11 patients with small defects (computer score < 7.0), infarcts involved < 20% of LV myocardium. Although scintigrams with large defects predicted a critical loss of myocardium in over 60% of our patients, they included an important second group, in which the scintigraphic defect appeared to reflect a small infarct and a large surrounding area of reversibly ischemic myocardium.