We have used extracorporeal liver perfusion (ECLP) to aid in the management of three patients with fulminant hepatic failure (FHF). Organs were used for ECLP only if they would have gone otherwise unused through United Network for Organ Sharing. In all three patients treated, serial serum bilirubin and arterial ammonia values trended toward the normal range. The neurologic examinations improved dramatically in two patients, and metabolic function of the extracorporeally perfused livers was unequivocally demonstrated by the clearance of theophylline in the last two patients. Two patients ultimately had successful liver transplants, whereas the third patient failed to improve neurologically despite evidence of metabolic function by the extracorporeally perfused liver, and died 7 days after ECLP was discontinued, from pulmonary and renal failure. These studies suggest that, 30 yr after initial clinical trials, ECLP can be applied safely without the need for arterial access 1) as a bridge to transplantation, 2) to assess whether patients in FHF will benefit from improved hepatic function and therefore transplantation, and 3) potentially, to evaluate the "usability" of questionable donor organs.