Since Ca-mediated electrophysiological phenomena seem to be important in the generation of various arrhythmias, we quantitatively compared the effects of quinidine, disopyramide, procainamide, lidocaine. propranolol, and etafenone, a new coronary vasodilator with antiarrhythmic properties, on Na and Ca channels in normal and depolarized guinea pig atria. The maximum rate of rise of the normal action potential and the amplitude of the depolarized, Ca-mediated action potential were measured to examine the Na and Ca channel activity, respectively. In both preparations, the contractile force was determined concomitantly in order to establish the role of Ca influx in the inotropic effects of the drugs. All six drugs suppressed the Na channel, the effect being strongest with etafenone. followed in order by quinidine, propranolol, disopyramide, lidocaine, and procainamide. Only quinidine. disopyramide, and propranolol suppressed the Ca channel and only in concentrations higher than those required to block the Na channel. Etafenone and procainamide increased Ca influx, while lidocaine had no effect on it. The negative inotropic effects of propranolol and disopyramide may be due to decreases in Ca influx, but the other drugs seem to have other mechanisms for their inotropic effects