The distribution of the coronary collateral circulation is an important determinant of the myocardial response to acute coronary artery occlusion. The dog shows an unequal response across the ventricular wall, whereas the pig seems to have more uniform transmural changes. This study was undertaken to compare the metabolic and blood flow response in pigs and dogs to acute occlusion of the circumflex artery. Microspheres (8-10 micron) were used to determine control blood flow and flow 5 min after occlusion. A transmural tissue sample from the center of the ischemic zone was taken at 8 min after occlusion, and inner, middle, and outer layers were analyzed for high-energy phosphates and lactate. The remainder of the heart was analyzed for microsphere distribution. The epicardium in the dog showed less severe damage than the subendocardium. High-energy phosphates were higher and lactate lower in this region. In the pig high-energy phosphates and lactate were the same in the subepicardium and subendocardium. Blood flow to regions surrounding the central ischemic zone in pigs was generally uniform across the ventricular wall or greater in the inner wall than in the outer wall. These results verify that dogs as a group have a greater subepicardial protection during coronary artery occlusion. Pigs, however, demonstrate uniform ischemia or even slightly less severe ischemia in the subendocardium in regions of restricted blood flow.