The depression of Vmax of the action potential in guinea-pig ventricular muscle by aprindine and quanidine was compared. Aprindine caused a more pronounced rate-dependent block (Kd = 10(-6) M at 3.3 Hz) than did quinidine (Kd = 1.6 X 10(-5) M at 3.3 Hz). Aprindine shifted the relationship between Vmax and resting potential to a more negative potential (mean 9.2 mV: 10 microM) than did quinidine (mean 5.7 mV: 10 microM). In addition, aprindine caused a more pronounced resting block (Kd = 1.3 X 10(-5) M) than quinidine (Kd = 8.6 X 10(-5) M). It is concluded that aprindine has a higher affinity for activated and/or inactivated and resting state channels than quinidine, making channels unavailable for conduction upon activation.