Fetal brain temperature has been found to decrease during hypoxia, strongly suggesting a reduction in cerebral O2 consumption and increases in cerebral blood flow. These responses may protect the brain in part against hypoxic injury. This study was undertaken to examine whether these compensatory mechanisms are lost during fetal hyperthermia. Intermittent fetal hypoxemia was induced by administering low-O2 gas mixtures to nine near-term ewes. Fetal brain and body core temperature responses were measured with and without fetal hyperthermia induced by circulating warm water through a plastic coil looped about the fetus in utero. In normothermic fetuses, fetal brain temperature relative to core decreased during a 30-minute period of hypoxia and then returned to normal during recovery. This response may be explained by a combination of cerebral hypometabolism and increased cerebral blood flow. However, in hyperthermic fetuses (intrauterine warming for 1 hour, raising body core and brain temperatures 0.66 +/- 0.06 and 0.61 +/- 0.10 C, respectively) a subsequent period of hypoxia no longer induced a reduction in brain temperature relative to body core. When temperature of the fetal sheep is elevated, as may occur with maternal fever, prolonged exercise, and elevated environmental temperatures, the fetal brain is less well protected against hypoxic injury.