The optimal therapeutic approach for the patient with refractory generalized status epilepticus remains to be defined. We describe four patients with refractory generalized status epilepticus who were successfully treated with intravenous midazolam. Each patient had prolonged convulsive status epilepticus unresponsive to standard doses of intravenous benzodiazepines, phenytoin, and phenobarbital. The patients subsequently received midazolam administered as an intravenous bolus (200 micrograms/kg) followed by a continuous infusion (0.75 to 11 micrograms/kg/min) lasting 8 hours to 10 days. Clinical examination and scalp electroencephalographic monitoring documented the cessation of seizure activity within minutes of the loading dose in all patients. No significant adverse effects occurred during midazolam treatment. The one patient with prolonged midazolam infusion required fluid boluses and pressors for moderate hypotension, and the remainder of the patients safely tolerated midazolam despite preexistent hemodynamic instability. All patients recovered and maintained good seizure control. Intravenous midazolam appears to be an effective treatment for refractory generalized status epilepticus, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia.