A study was undertaken to determine if gut flora contribute to the pathophysiology of experimental canine heatstroke. Fifty animals in four groups were anesthetized with sodium pentobarbital (25 mg/kg) intravenously. An air temperature of 42-46 degrees C was maintained adjacent to the dog with a water-heated blanket for approximately 2 h until rectal temperatures rose to 43.5 +/- 0.4 degrees C. Animals were then cooled passively in room air (28 degrees C, 20% RH) until death or until 18 h elapsed, and were euthanized. Reduction of intestine stool and bacterial contents with antibiotics, cathartics, and enemas prior to heatstroke increased the incidence of 18-h survival from 20.0% to 70.6%; antibiotics administered after heatstroke did not alter the incidence of survival over control values. These data suggest that gut flora, presumably through endotoxemia, contribute to the evolution of heatstroke pathophysiology.