In the present study, subtotal hepatectomy was evaluated as a model of acute liver failure in the rat. Sprague-Dawley rats, weighing 250–300 g, underwent hepatectomy under varying basal conditions of temperature and glucose administration. Rats operated and maintained postoperatively at ambient temperature (25 °C external environment) developed hypothermia with a rate of return to normal temperature which was related to the extent of hepatectomy and the availability of glucose postoperatively. However, no significant difference in survival was observed between groups maintained at ambient temperature and those whose core temperature was maintained at 37 °C by passive external warming. Severe hypoglycemia was observed in rats undergoing 90 and 95% hepatectomy without glucose postoperatively. With 20% glucose available in drinking water the mortality of 90% hepatectomy was reduced from 95 to 40% (p < 0.0001). With increase of the hepatectomy to 95%, 90% mortality was observed despite glucose support. Transplantation of 4 × 107 isolated syngeneic hepatocytes intraperitoneally at the time of hepatectomy did not increase survival after 90 or 95% hepatectomy; addition of testosterone therapy did not improve survival either alone or with hepatocyte transplantation. In this study, hepatectomy exceeding 90% was lethal and did not respond to the supportive measures provided. Hepatocyte transplantation and testosterone pretreatment, both therapies which are thought to increase regeneration, were ineffective in improving survival in this resection m