Antiarrhythmic drugs are often required in patients with implantable cardioverter-defibrillator devices. Prior evidence suggests that drugs modulate defibrillation energy requirements by altering ion channel activity. To evaluate the effects of calcium ion channel activity on internal defibrillation energy requirements, the calcium antagonist verapamil and Bay K 8644, a calcium channel activator, were investigated in 30 open-chest, pentobarbital-anesthetized dogs. Defibrillation energies were applied across two epicardial patch electrodes. The likelihood of successful defibrillation was determined at various shock energy levels, and the 50 and 90% effective energy doses were calculated using nonlinear regression. In saline control experiments (n = 10), the stability of the preparation throughout the 6-h duration of the experiments could be demonstrated. Verapamil administration (n = 10) infused to a mean plasma concentration of 69 ng/ml increased the 50 and 90% effective defibrillation energies by 41 and 43% (p less than 0.05), respectively, and to a mean plasma verapamil concentration of 170 ng/ml by 95 and 75% (p less than 0.01), respectively. The mean cycle length during ventricular fibrillation decreased with verapamil and was inversely related to the change in defibrillation energy requirement. Administration of Bay K 8644 (n = 10) produced a slight increase in the 50% effective defibrillation energy (25%; p less than 0.05) and 90% effective defibrillation energy (17%; n.s.). The electrophysiologic effects of verapamil were neither prevented nor reversed by Bay K 8644. In conclusion, intravenous verapamil administration caused an increase in defibrillation energy requirements, but the mechanism by which verapamil exerted this effect remains unclear. These experimental data suggest that verapamil should be used in patients with automatic implantable cardioverter-defibrillator devices only after individual testing.