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.