Hepatic encephalopathy is a complex neuropsychiatric syndrome associated with acute, subacute and chronic liver failure, involving increased neural inhibition by activation of the GABA/benzodiazepine inhibitory neurotransmitter system. Improvement by GABA and benzodiazepine receptor antagonists as well as by chloride ionophore blockers has been shown in animal experiments. Recent reports indicate that flumazenil may improve hepatic encephalopathy in man. To date 46 episodes of HE in 41 patients have been treated with flumazenil with a short term success rate of 72%. Most of the patients were screened for exogenous benzodiazepines and found negative. These interesting observations should now be investigated in a randomised double-blind controlled study in patients with HE to evaluate the efficiency of this therapy.