The first clinical use of the Excorp Medical Bioartificial Liver Support System (BLSS) in support of a 41-year-old African-American female with fulminant hepatic failure is described. The BLSS is currently in a Phase I/II safety evaluation at the University of Pittsburgh/UPMC System. Inclusion criteria for the study are patients with acute liver failure, any etiology, presenting with encephalopathy deteriorating beyond Parson's Grade 2. The BLSS consists of a blood pump; a heat exchanger to control blood temperature; an oxygenator to control oxygenation and pH; a bioreactor; and associated pressure and flow alarm systems. Patient liver support is provided by 70–100 g of porcine liver cells housed in the hollow fiber bioreactor. The patient exhibited transient hypotension and thrombocytopenia at initiation of perfusion. The only unanticipated safety event was a lowering of patient glucose level at the onset of perfusion with the BLSS that was treatable with intravenous glucose administration. Moderate changes in blood biochemistries pre- and post perfusion are indicative of liver support being provided by the BLSS. While the initial experience with the BLSS is encouraging, completion of the Phase I/II study is required in order to more fully understand the safety aspects of the BLSS.