We investigated the effect of mild whole-body hyperthermia (40 degrees C) on a permanent middle cerebral artery occlusion (MCAo) model in Fisher rats by subjecting them to MCAo under the following conditions: (1) normothermia (n = 20); (2) hyperthermia (n = 14) before (1 hour), during, and after (1 hour) MCAo; and (3) post-MCAo hyperthermia (n = 14) for 1 hour. We measured brain and body temperatures during the experiment using micro-thermocouples and blood-brain-barrier (BBB) permeability using Evans blue staining of the brain. We measured the volume of the infarcted brain tissue 4 days after MCAo. We detected no differences in BBB permeability among three groups. The volume of infarcted tissue was significantly greater (p less than 0.05) for the two groups of hyperthermic animals than the normothermic animals. Our data suggest that mild hyperthermia, both during and after induction of ischemia, has a detrimental effect on the ischemic infarct volume in this model.