The antiarrhythmic activity of amitriptyline, a tricyclic antidepressant, e evaluated in anesthetized dogs 24 h after coronary occlusion, during the period of spontaneous ventricular arrhythmias. In all experiments amitriptyline was administered i.v. in encremental doses of 0.3 mg/kg at 1 min intervals until a conversion to normal sinus rhythm was evident. Amitriptyline administration resulted in conversion of the ventricular arrhythmia to a normal sinus rhythm in 100% of the animals tested at a mean dose of 1.3 ± 0.1 mg/kg. Smaller doses also resulted in a dose-related decrease in non-sinus nodal pacemaker activity. Lidocaine, when administered to the same group of animals, produced a reduction of ectopic pacemaker activity, but did not eliminate it at a cumulative dose of 2 mg/kg. Antiarrhythmic doses of amitriptyline did not produce significant changes in arterial blood pressure, cardiac output or electocardiographic parameters associated with atrioventricular or intraventricular conduction. The results of this study suggest that at vary low doses amitriptyline may be an effective antiarrhythmic agent in ventricular arrhythmias associated with myocardial ischemia. © 1978.