Valproate can be associated to hyperammonemic encephalopathy, characterized by fluctuating sudden-onset alterations of sensorium, focal symptoms and an increase in the frequency of seizures. We report a 78 year-old female using valproate 1,000 mg/ day for 10 months for the treatment to tonic-clonic seizures. She was admitted on three occasions in the last fourth months for self limited clouding of sensorium. Laboratory, imaging and electroencephalographic studies were non-contributory Blood ammonia levels were 123 microg/dl (normal: 15-50 microg/dl). Due to the possibility of a hyperammonemic encephalopathy secondary to valproate, the drug was discontinued and she was treated with lactulose and intravenous L-carnitine, 1 g/day The patient showed a complete recovery within 48 hours. This drug-associated encephalopathy is a reversible but potentially fatal cause, probably underdiagnosed, that requires a high index of suspicion.