The purpose of this study was to determine whether cerebral cortical microvascular responses to platelet-derived vasoactive substances are altered after normothermic cardiopulmonary bypass (CPB), and whether these alterations are modified by moderate hypothermia. Pigs were placed on normothermic CPB (37 degrees C) for 2 hours and then perfused off CPB with normothermic blood for either 15 minutes (n = 8) or 60 minutes (n = 6). Another group was placed on moderately hypothermic CPB (25 degrees C) for 2 hours and then perfused off CPB at 37 degrees C for 15 minutes (n = 6). Alphastat pH management was used. In vitro responses of isolated cortical cerebral arterioles (90 to 170 microns internal diameter) to platelet-derived vasoactive substances were examined in a pressurized no-flow state with videomicroscopy. Microvessels from noninstrumented pigs (n = 14) were used as controls for in vitro studies. Cerebrovascular resistance and internal carotid artery blood flow were similar 15 minutes after CPB in both normothermic and hypothermic groups. However, relaxations of microvessels to adenosine 5' diphosphate or serotonin were reduced in vessels from both groups. One hour of after CPB cerebral perfusion did not change this pattern of altered vascular reactivity. Hypothermia caused a partial but significant reduction in impairment of responses to adenosine 5' diphosphate and serotonin. Microvascular relaxation to the endothelium-independent agent sodium nitroprusside and contraction to a thromboxane A2 analog were similar in all experimental groups, suggesting normal vascular smooth muscle responsiveness. This study demonstrates that normothermic extracorporeal circulation reduces endothelium-dependent relaxation responses to products of platelet activation in the cerebral microcirculation. Moderate hypothermia attenuates the CPB-induced impairment of endothelium-dependent relaxation, but has no effect on baseline cerebral blood flow after rewarming.