The effect of nortriptyline against ventricular arrhythmias was determined in 16 cardiac patients with 30 or more ventricular premature depolarizations per hour. Nortriptyline was administered orally, 0.5 mg/kg body weight per day, and increased by 0.5 mg/kg per day every third day until ventricular premature depolarizations were suppressed (≥80%), adverse effects occurred or a total daily dose of 3.5 mg/kg per day was given. Each patient had daily 24 hour continuous electrocardiograms, 12 lead standard electrocardiograms and physical examination; blood pressure was measured in the supine and standing position four times a day. Each patient also had radionuclide angiography at rest to measure ejection fraction before and at the effective or maximal dose. Thirteen patients (81%) had an antiarrhythmic response and 11 met the study criterion of at least 80% improvement. Doses ranged from 50 to 200 mg/day (mean 111 ± 45), steady state plasma concentration ranged from 46 to 410 ng/ml (mean 153 ± 96) and half-life of elimination of nortriptyline was 4 to 22 hours (mean 13 ± 4). Administration of nortriptyline did not depress mean ejection fraction (before 42 ± 12%, after 41 ± 12%); it was associated with an orthostatic decrease in systolic blood pressure (mean -13 ± 13 mm Hg). Nortriptyline is an effective antiarrhythmic agent which may be given twice a day even in patients with impaired ventricular function.