To assess the adequacy of tissue oxygenation in fulminant hepatic failure, we measured arterial oxygen delivery, the affinity of hemoglobin for oxygen, mixed venous oxygen tension, and lactate concentration in 32 patients suffering grade IV encephalopathy. In the patients who died, median systemic vascular resistance and oxygen extraction ratio were significantly (p less than .005) lower than in those who survived (1268 vs. 1866 dyne . sec/cm5 . m2 and 20% vs. 25%, respectively) despite a significantly (p less than .01) greater oxygen delivery in the former group (716 vs. 570 ml/min . m2). Furthermore, nonsurvivors had significantly greater in vivo P50 and mixed venous lactate values (31 vs. 29.5 torr [p less than .02], and 5.1 vs 3.0 mmol/L [p less than .05], respectively). Only in survivors was the in vivo P50 related to the oxygen extraction ratio (r = 0.68 and p less than .01, compared with r = 0.03 in nonsurvivors). These results suggest that the fall in systemic vascular resistance is related to some form of arteriovenous shunting and that this is more severe in patients who die. The subsequent development of tissue hypoxia is an important prognostic factor in fulminant hepatic failure that may contribute to the occurrence of irreversible multiple organ failure.