Since pathological changes in the liver are among the consistent findings in humans subsequent to heatstroke, specimens were taken from the liver in rats during a study to assess the rat as a model for human heatstroke. Tissues from four groups of rats were processed for light and electron microscopy. The groups consisted of control rats, rats run to exhaustion at 5 C, rats exhausted at 26 C, and rats restrained at 41.5 C until their rectal temperatures reached 42.3 C. Exhaustive exercise at 5 C produced neither fatalities nor pathological changes in the livers. Exhaustive exercise at 26 C and restraint at 41.5 C were fatal for most rats. Histological and/or ultrastructural changes, which included centrilobular necrosis, vacuolization and diminution of hepatocellular microvilli, and loss of sinusoidal endothelium, were observed in livers from rats that were run to exhaustion at 26 C and from those rats restrained at 41.5 C. This work supports the validity of the rat model, since human heatstroke results in similar hepatic changes.