Alcoholic cirrhosis is frequently associated with episodes of portal-systemic encephalopathy (PSE). There is a growing body of evidence to suggest that the so called "peripheral-type" (non GABA-related) benzodiazepine receptors are modified in PSE. Peripheral-type benzodiazepine receptors are localized on the outer mitochondrial membrane in many tissues including brain where they are highly concentrated in astrocytes. PSE is characterized neuropathologically by astrocytic rather than neuronal changes. Densities of peripheral-type benzodiazepine receptors are significantly increased in autopsied brain tissue from alcoholic cirrhotic patients who died in hepatic coma and in the brains of rats following portacaval anastomosis. Endogenous peptide ligands for these receptors are increased in the CNS in clinical and experimental PSE.