We report a novel one-stage technique of total hepatectomy in the rat, in which the liver is replaced by an autologous prosthesis. This prosthesis is obtained from a donor rat, and consists of the subhepatic vena cava and the left renal vein harvested en block. This graft is sutured with the subdiaphragmatic cava and linked with cuffs to the subhepatic vena cava and the portal vein in the donor rat. This procedure is associated with a very low operative mortality. Rats with glucose and plasma-expander infusions survived for a mean time of 23 +/- 9 hr. This technique of total hepatectomy can be considered a valid and reproducible model of true anhepaty for metabolic and survival studies with liver support systems.