We studied the mode of antiarrhythmic action of melperone by His bundle electrography combined with programmed electrical stimulation in 21 pentobarbital anaesthetized dogs. Melperone alone (0.5 to 12.5 mg/kg) as well as melperone after sympathetic and parasympathetic blockade caused a dose-dependent increase in the ventricular and, even more, the atrial effective refractory period without affecting atrial and ventricular conduction times. Melperone shortened the atrioventricular nodal conduction time regardless of sympathetic and parasympathetic blockade. We conclude that the antiarrhythmic effect of melperone is most likely primarily due to a direct class 111 antiarrhythmic action.