SummaryElectrophysiological properties of quinidine and the two isomers of propranolol were compared in pentobarbital-anesthetized dogs using His bundle recordings and programmed stimulation in order to differentiate the effects resulting from β-blockade from those related to nonspecific membrane-stabilizing effects. Quinidine in the plasma concentration range of 2.7–20 μM/liter resulted in concentration-dependent increases in atrionodal and His-Purkinje system conduction times and in the atrial effective refractory period. Quinidine did not produce any significant concentration-dependent change in atrioventricular (AV) nodal and ventricular refractory periods, sinus node automaticity, or QTc interval duration. Propranolol isomers in concentration range of 0.03–0.85 μM/liter produced a concentration-dependent increase in atrionodal conduction time but exerted no significant effect on His-Purkinje conduction time, QTc duration, or ventricular refractory period. Both isomers increased the atrial effective refractory period, but with slopes of concentration-response regression lines which were significantly different from those of quinidine. Onlyl-propranolol produced concentration-dependent increases in AV nodal refractory period, Wenckebach cycle length, and sinus node recovery time. These results suggest that the electrophysiological effects of propranolol isomers are related to β-blockade and are significantly different from those resulting from the membrane-stabilizing effect of quinidine.