Hepatic encephalopathy (HE) is a complex reversible syndrome that can progress to coma. Recently, behavioral and electrophysiologic ameliorations of HE have been reported to occur in animal models of fulminant hepatic failure (FHF) and, in uncontrolled studies, in a majority of patients with FHF or cirrhosis following the intravenous administration of the benzodiazepine (BZ) receptor antagonist, flumazenil. These observations, while not excluding a role for other mechanisms in the mediation of HE, raise the possibility that an endogenous BZ receptor ligand with agonist properties may contribute to the manifestations of HE by allosterically potentiating GABA-mediated neurotransmission.