A previously healthy patient became acutely encephalopathic, with complete disorientation and amnesia, several days after the onset of thoracic herpes zoster. She had transiently abnormal electroencephalographic results, abnormalities on radionuclide brain scanning, and cerebrospinal fluid pleocytosis. There was no evidence of a toxic/metabolic encephalopathy except for a mildly elevated ammonia level. Intravenously administered acyclovir (30 mg/kg per day) induced a dramatic response, with complete resolution of the encephalopathy within 72 hours and normalization of the electroencephalographic results. The scant clinical experience with the successful use of acyclovir in the treatment of herpes zoster-associated encephalitis is reviewed.