We evaluated the effect of induced whole-body hyperthermia on renal tissue blood flow in dogs by the hydrogen clearance technique. The heart rate increased significantly at 41°C and above, whereas blood pressure decreased significantly at 43°C. Cardiac output increased significantly at 41°C and above, whereas renal arterial blood flow tended to decrease above 41°C. Although renal cortical tissue blood flow significantly decreased at 42°C, renal medullary tissue blood flow showed no marked changes with increasing temperature. Redistribution of blood flow within the kidney was therefore apparent during hyperthermia. A significant decrease was observed in the partial pressure of oxygen in arterial blood, as well as in oxygen saturation of arterial, renal venous, and central venous blood, suggesting that hypoxia also may have occurred in the kidneys. Several animals showed an increase in the ratio of thromboxane B₂ to 6-keto-PGF₁ α in renal venous blood at 42°C. These data indicate that renal injury during hyperthermia may result from decreased tissue blood flow in the renal cortex and hypoxia in renal tissue. Furthermore, metabolites of arachidonic acid, such as thromboxanes, may help to mediate the changes in tissue blood flow.