Brain edema and intracranial hypertension are a major cause of death in fulminant hepatic failure. We have shown that brain water measured in rats after hepatic devascularization (portacaval anastomosis followed in 24 to 48 hr by ligation of the hepatic artery) increases with the progression of encephalopathy. In this study, we examined whether intracranial hypertension develops in this model of fulminant hepatic failure. Using a fiberoptic pressure transducer, intracranial pressure rose from 3.3 ± 1.1 mm Hg to 23.7 ± 2.7 mm Hg (mean ± S.E.M.) by the time the corneal reflex was lost; intracranial pressure was unchanged in control rats. Immediately after ligation of the hepatic artery, intracranial pressure was normal and remained stable until the last hours of the experiment, when it progressively rose, suggesting a loss of intracranial compliance. In addition, sudden and short episodes of marked increases in intracranial pressure (>50 mm Hg) not related to seizure activity markedly decreased cerebral perfusion pressure. Internal carotid artery blood flow, an indirect measure of cerebral perfusion, decreased 29% ± 12% by the end of the experiment. The time elapsed from ligation of the hepatic artery until loss of the corneal reflex (range 340 to 940 min) was related to the change in cerebral perfusion pressure, suggesting that an increase in systemic arterial pressure at the time of the initial rise in intracranial pressure may result in an increased length of survival. In this animal model, widely used to study the pathogenesis of hepatic encephalopathy, intracranial hypertension invariably appears in the terminal phase of the course. The development of intracranial pressure waves may be an indication that brain herniation is imminent. (HEPATOLOGY 1991;14:715–720.)