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It is not yet clear if benzodiazepine receptor ligands, implicated in the pathophysiology of hepatic coma, also have a role in subclinical cognitive or neurophysiological alterations in cirrhotic patients. Therefore, we carried out a double-blind, placebo-controlled study to evaluate the effectiveness of flumazenil, a benzodiazepine antagonist, on brainstem auditory evoked responses and on the number connection test in cirrhotic patients with subclinical neurophysiological or cognitive alterations. Thirteen cirrhotic subjects with subclinical neurophysiological or cognitive alterations were studied. A total of 3 mg of flumazenil or saline was infused intravenously. Before and after the infusion, the number connection test was administered and brainstem auditory evoked responses recorded. After 72 h, patients were crossed over. Flumazenil did not influence brainstem auditory evoked responses or the number connection test. A screening test for benzodiazepines was negative in all subjects. We conclude that benzodiazepine receptor ligands have a negligible role, if any, in the pathophysiology of sub-clinical neurophysiological or cognitive alterations of cirrhotic patients.