Sedative-hypnotic antiepileptic drugs have potentially toxic effects, but their removal is often thought to be difficult and dangerous. We completely withdrew all barbiturates and benzodiazepines from 78 patients with intractable epilepsy (48 inpatients and 30 outpatients). Initially, 19 patients had plasma levels of sedative drugs above the therapeutic range; 28 were taking more than one of these drugs. Dosages of nonsedative antiepileptic drugs were adjusted to provide optimal seizure control. After 6 months of outpatient follow-up, 69 patients remained on a nonsedative regimen: 35 (51%) showed improvement in both drug toxicity and seizure control, 13 (19%) in toxicity alone, 8 (12%) in seizure control alone; 12 (16%) were unchanged, and 1 was worse. Of 9 patients restarted on sedative antiepileptic drugs by their private physicians, 4 had more toxic symptoms than at discharge, 1 had more frequent seizures, 3 were unchanged, and 1, who had had a temporal lobectomy after drug withdrawal, had less frequent seizures. Sedative drugs are not necessary for optimal seizure control, even in intractable epilepsy, and they may be safely withdrawn.