This report describes the efficacy of syngeneic hepatocyte transplantation in an anoxic model and of xenogeneic (rabbit and porcine) hepatocyte transplantation in a toxic model of fulminant hepatic failure in the rat. Lewis strain rats that received 4 X 10(7) hepatocytes intraperitoneally at 48 hours after hepatic artery ligation had a significantly improved survival rate (79%, n = 14) when compared with control animals (38%, n = 21, P less than 0.05). Xenogeneic hepatocytes (4 X 10(7) cells/rat) given intraperitoneally to D-galactosamine-poisoned Lewis rats at 48 hours after toxin administration were able to significantly improve survival rate as compared with controls (71% versus 14%, n = 14, P less than 0.01 for rabbit; and 75%, n = 14 versus 12.5%, n = 16, P less than 0.001 for porcine). Although an increase in in vivo cytotoxicity could be demonstrated after procine hepatocyte transplantation, no adverse clinical effects were observed. The methodology for the harvest and storage of large numbers of hepatocytes from a large animal liver has been developed, and it is now feasible to proceed to the clinical application of hepatocyte transplantation for human fulminant hepatic failure.