The purpose of this study was (1) to establish the maximal interval between the onset of ischemia and reperfusion that would permit a decrease in the size of infarction, and (2) to evaluate the relation between changes in infarct size and preservation of cardiac function. Studies were carried out in 19 dogs of which 13 had temporary (1 to 3 hours) occlusion of the left anterior descending coronary artery. The hospital course of 15 patients of whom 13 underwent myocardial revascularization within 8 hours of acute infarction was also reviewed. In dogs, the eventual pathologic infarct size was significantly reduced if reperfusion was performed within 2 hours of ischemia. After 2 hours of ischemia, the revascularized segment remained dyskinetic on angiographic assessment and cardiac function was depressed. After 3 hours of ischemia, in spite of a patent coronary artery, the extent of infarct and dykinesia was greater than during ligation of the left anterior descending coronary artery. In patients, small infarcts developed with revascularization performed more than 4 hours after infarction but with revascularization of the left anterior descending coronary artery the size of the dyskinetic area (as assessed with angiography) was similar to that in patients with a closed graft to the left anterior descending coronary artery but with a patent graft to its diagonal branch. In all patients after revascularization the extent of the left ventricular dyskinetic area was smaller and cardiac function was significantly better than in patient who did not receive revascularization for complete occlusion of the left anterior descending coronary artery. In spite of successful revascularization, electrocardiographic evidence of transmural infarction persisted postoperatively. It is concluded that reperfusion of an area of myocardium that has been ischemic for less than 2 hours in dogs or less than 4 hours in man may lead to a significant reduction in the extent of infarction as well as improvement in cardiac function. However, the revascularized area remains angiographically dyskinetic and electrocardiographically abnormal.