This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope labeled microspheres, 7-10 μm in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 ± 0.03 (SE), 0.39 ± 0.05, 0.39 ± 0.04, and 0.53 ± 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmural layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured.