This study examined the effects of the diethylamino analog of ethmozin (ethacizin) (1 mg/kg i.v.) on the spontaneous and reflexly elicited efferent activity in thoracic cardiac sympathetic and parasympathetic nerves. Nitroglycerin and phenylephrine (4 and 8 micrograms/kg i.v.) were administered to 15 anesthetized mongrel dogs while monitoring blood pressure and heart rate. In each dog two cardiac nerves were isolated and efferent neurograms were recorded simultaneously and analyzed by microprocessor. Ethacizin significantly attenuated the spontaneous sympathetic efferent activity in both left and right, preganglionic (n = 8) and postganglionic (n = 14) sympathetic nerves to the heart. In contrast, reflex changes in sympathetic activity elicited by baroreceptor challenges were not affected by ethacizin. Also, ethacizin did not significantly affect either spontaneous or baroreceptor reflex-induced parasympathetic efferent activities in eight preganglionic nerves. Thus, this new phenothiazine derivative may exert part of its antiarrhythmic action through a reduction of the spontaneous sympathetic tonic discharges to the heart. The fact that ethacizin reduced neither the reflex-induced changes in sympathetic or parasympathetic activities nor influenced the tonic vagal discharges further suggests that the compound is not likely to interfere with reflexly mediated cardiovascular adaptive changes.