Intra-atrial, ventricular septal and left ventricular free wall conduction rates as well as lead II EKG intervals and heart rate were measured in pentobarbital-anesthetized, open-chest dogs given increasing doses of either trazodone (0.3-30 mg/kg) or imipramine (0.1-10 mg/kg) intravenously. Conduction intervals were measured during periods of spontaneous nodal rhythm or fixed rate (150 b/min) of atrial pacing. Trazodone, at cumulative doses up to 44.3 mg/kg, did not significantly depress any measured index of cardiac conduction but did lower heart rate (36%) and prolong the Q-Tc interval (19%). Imipramine, particularly at doses of 3 and 10 mg/kg, caused bradycardia (32%) and significantly slowed both atrial (23-46%) and ventricular (21-55%) conduction as well as repolarization interval (14-35%). The data indicate the differing effects of these two compounds on the heart and represent suggestive evidence of the potentially greater safety of trazodone as a new and structurally distinct antidepressant drug.