Recent infarcts were compared with the anatomic boundaries of the involved vascular bed in human hearts to determine the amount and location of necrosis in relation to the myocardium at risk. The coronary arteries were injected with BaSo4 in 18 human hearts with 3-16-day-old infarcts. Thin (3-4-mm) slices were cut at 10-15 min intervals, photographed, x-rayed and used for histologic analysis. Infarct outlines were traced from gross photographs using histologic confirmation of infarct boundaries, and the vascular bed was independently traced from the x-rays. Ischemic bed size and infarct size were then calculated by computerized planimetry. Infarct size ranged from 13-72% of the left ventricle (mean 30 ± 3.6%) and was linearly related to the size of the occluded vascular bed (r = 0.93). However, the infarcts were always smaller than the occluded beds. They involved 50-88% of the ischemic bed (mean 69 ± 3.0%) due to variation in the transmural extent of necrosis. A lateral zone of viable muscle within the ischemic bed was present but consistently narrow (mean 1.7 ± 0.3 mm) so that the infarcts involved 93 ± 2.3% of the width of the bed at risk. Thus, ischemic bed size is a major determinant of infarct size in fatal human infarcts. When natural limitation of infarct size occurs, it is due primarily to limitation of the transmural extent of necrosis.