We investigated the effect of post-ischemic 30 degrees C hypothermia on transient middle cerebral artery (MCA) occlusion in the rat. Male Wistar rats (n = 27) were subjected MCA occlusion for 2 h by inserting a nylon filament into the internal carotid artery. Three groups of animals were studied: 1) normothermic ischemia and normothermic reperfusion (n = 13), 2) normothermic ischemia and 1 h of hypothermic reperfusion (n = 6), 3) normothermic ischemia and 3 h of hypothermic reperfusion (n = 6); monitoring of cerebral temperatures were performed on two additional rats. The animals were sacrificed after one week, and coronal sections were obtained and stained with hematoxylin and eosin (H/E) for histopathological examination and determination of infarct volume. The data indicate that both normothermic reperfusion and 1 h hypothermic reperfusion groups exhibited similar infarct volumes in the cortex and the basal ganglia, respectively (P > 0.1). The 3 h post-ischemic hypothermia group revealed a significant decrease in infarct volume in the cortex compared to the normothermic group (P < 0.05). However, the infarct volume of the basal ganglia was not significantly lessened by the 3 h post-ischemic hypothermia. Thus 3 h post-ischemic hypothermia provides preferential reduction of cell damage in the cortex, from 2 h of MCA occlusion in the rat.