The effect of propylene glycol, benzyl alcohol, quinidine, and procainamide on the effective refractory period of isolated rabbit atria were compared. The lengthening of effective refractory period reached its maximum at approximately 10 min for solvents and 40 to 50 min for quinidine and procainamide. The slopes of the effective refractory period curves were similar for propylene glycol and benzyl alcohol. The slopes of the effective refractory period curves for quinidine and procainamide were similar, but they differed from those obtained with propylene glycol and benzyl alcohol. These differences suggest that propylene glycol and benzyl alcohol lengthen the effective refractory period by different mechanism than that of quinidine and procainamide. The effective dose 50% required for lengthening the effective refractory period is 20-fold greater for quinidine than for procainamide with similar relative responsiveness. On the other hand, the solvents showed low affinity and low relative responsiveness, although the combination of propylene glycol and benzyl alcohol showed similar relative responsiveness to procainamide. Despite the fact that these solvents have a lower antiarrhythmic potency, their therapeutic index is 5- to 50-fold greater than quinidine and/or procainamide.