To determine whether coronary thrombi can be detected scintigraphically after acute myocardial infarction, 24 patients were studied with a new method employing indium-111-labeled platelets and technetium-99m-labeled red blood cells. Nine patients with suspected infarction were evaluated initially within 9 hours of the onset of symptoms and again 18 to 24 hours after onset. Eight patients with neurologic symptoms but without overt cardiac disease and seven patients with angina but without infarction served as unmatched control subjects. Foci of net indium accumulation were detected after image processing that incorporated subtraction of blood pool activity. Carotid and pulmonary artery reference regions, in which blood pool activity is high and active platelet deposition unlikely, were used to correct digitized cardiac scintigrams for indium-111 platelet activity in the blood pool. In patients with infarction, distinct foci of net indium accumulation were present in regions corresponding to the coronary artery supplying ischemic zones. This occurred in seven of eight patients at the time of the earliest evaluation (5.6 ± 3.3 hours [mean ± SD] after the onset of symptoms) and in eight of nine patients at the time of subsequent imaging (23.6 ±1.9 hours after onset). Only 1 of the 15 control patients exhibited a cardiac focus of net indium accumulation. The percent of indium excess (100 [total indium-111 activity-blood pool indium-111 activity]/blood pool indium-111 activity) within the cardiac region measured (± SD) 16.8 ± 11.6% in all patients with myocardial infarction (19.1 ± 11.2% in those with visually identified foci) compared with 0.4 ± 4.3% in control patients (p < 0.001). This method permits early detection and sequential assessment of coronary artery thrombi. It should permit improved characterization of the role of platelets in the pathogenesis of acute manifestations of coronary vascular disease and improved evaluation of interventions designed to prevent or lyse coronary thrombi.