The sequential effects of reperfusion following acute intracoronary balloon occlusion were investigated in closed-chest anesthetized dogs by simultaneous measurement of hemodynamics and regional metabolism and histopathologic study. Simultaneous regional determinations of myocardial metabolic function were carried out in coronary-occluded and nonoccluded segments of the left ventricle. A 3-hour occlusion of the proximal left anterior descending coronary artery (LAD) resulted in significant decrease in cardiac function. Intitial reperfusion was marked by major washout of metabolites and development of frequently serious arrhythmias. Reperfusion following 3 hours of LAD occlusion led to futher deterioration in hemodynamics and metabolism: 30% of the dogs developed shock. Lactate extraction decreased further in the nonoccluded region and reached production levels in the occluded zone. Potassium loss increased in both zones. Oxygen extraction remained unchanged. Pathophysiologic examination of tissue specimens from the reperfused zone revealed microthrombi, patchy necrosis, fragmentation of myofibrils, vascular congestions, and hemorrhages.