Primidone, 50 to 1,000 mg/d, reduced the amplitude of essential tremor in both untreated and propranolol-treated patients. Low doses were as effective as high doses. Primidone decreased tremor more than propranolol. There was no correlation between therapeutic response and serum levels. Acute reactions to the initial dose and side effects of higher doses caused drug intolerance. A single oral dose (250 mg) decreased tremor by 60% 1 to 7 hours after ingestion, with stable serum primidone levels but no detectable phenobarbital levels. Tremor control was lost when phenobarbital was substituted for primidone. Primidone is an effective agent for the treatment of essential tremor.