The evolution and transmural distribution of coronary collateral blood flow in acute myocardial infarction was determined in 24 trained, unanesthetized dogs by injection of radioactive microspheres into the coronary circulation. Acute coronary artery occlusion resulted in a greater decrease in subendocardial flow than subepicardial flow in both the central and marginal zones of the infarct. Coronary collateral blood flow was distributed primarily to the marginal zone and to the subepicardium of the central zone of the infarct. The greatest increase in collateral flow occurred between 12 and 18 hr after coronary artery occlusion. By 24 hr after coronary occlusion, blood flow to all areas of the infarct except the subendocardium of the central zone had returned to near control levels. This disproportionate distribution of coronary collateral blood flow during the early stages of myocardial ischemic injury helps to explain the apparent lack of protection of the subendocardium by collateral flow.