The effect of acute intravenous administration and chronic oral loading of amiodarone on defibrillation threshold was evaluated in normal anesthetized dogs using implanted superior vena caval spring and left ventricular patch electrodes. The effect of oral loading with amiodorone was evaluated by comparing three groups of six dogs each that received either no drug, 200 mg/day for 9 days, or 400 mg/day for 9 days. Defibrillation threshold was evaluated by administering a fixed sequence of shocks with increasing energies until defibrillation was successful. Defibrillation was determined 13 times in each animal. The mean defibrillation threshold (plus or minus standard error of the mean) was 7.5 ± 0.3 J in the control group, 15.4 ± 0.6 J in the group receiving amiodarone 200 mg/day, and 17.9 ± 0.8 J for the group receiving 400 mg/day. These values are significantly different using analysis of variance and Tukey's test. The acute effect of intravenous amiodarone, 5 mg/Kg was evaluated in five dogs using each dog as its own control. The mean defibrillation threshold during control period was 10.8 ± 0.4 J, and during the first two hours after amiodarone administration was 10.8 ± 0.4 J. There was no significant difference. Thus, in this study oral administration of a loading dose of amiodarone comparable to that used in patients produced a dose dependent increase in defibrillation threshold, whereas no change in defibrillation threshold was observed acutely after intravenous administration.