The purpose of this retrospective study was to determine cerebral hemodynamic and metabolic changes in comatose patients with fulminant hepatic failure. Computerized tomography of the brain and cerebral blood flow measurements by the xenoncomputerized tomography scan or intravenous xenon-133 methods were obtained in 33 patients with fulminant hepatic failure. In a subgroup of 22 patients, arteriojugular venous oxygen content difference and cerebral metabolic rate for oxygen were determined. Carbon dioxide reactivity was tested in 17 patients, and intracranial pressure was recorded by an epidural monitor in 8 patients. Cerebral blood flow and arteriojugular venous oxygen content difference were adjusted to the average arterial carbon dioxide pressure of the sample (32 mm Hg). Adjusted cerebral blood flow varied from 16.5 to 94.7 ml/100 gm/min; 52 of the patients had reduced adjusted cerebral blood flows (less than 33 ml/100 gm/min), whereas 24 had hyperemic values (greater than 50 ml/100 gm/min). Patients with higher adjusted cerebral blood flows showed cerebral swelling on computerized tomography scan (p < 0.002), were in deeper coma (p < 0.05) and had greater mortality (p < 0.002). The adjusted arteriojugular venous oxygen content difference was negatively correlated with adjusted cerebral blood flow (r = −0.61, p < 0.002). The majority of patients with reduced adjusted cerebral blood flows had low adjusted arteriojugular venous oxygen content differences (less than 5 vol), indicating hyperemia rather than ischemia. The average cerebral metabolic rate for oxygen was 50 of normal (1.6 ± 0.4 ml/100 gm/min); even patients with low cerebral metabolic rates for oxygen recovered neurologically. Carbon dioxide reactivity was preserved in almost all patients, which argues for the effectiveness of hyperventilation in reducing blood flow. All four patients with elevated intracranial pressures (greater than 24 mm Hg) had increased adjusted cerebral blood flows; three of four patients with intracranial pressures less than 20 had reduced adjusted cerebral blood flows. These findings suggest that cerebral swelling, intracranial hypertension and cerebral hyperemia are poor prognostic signs in patients with fulminant hepatic failure. (Hepatology 1994; 19:80-87).