The purpose of this study was to determine the effect of the antiarrhythmic drugs lidocaine and bretylium on the minimal energy requirement for transthoracic defibrillation--the defibrillation threshold. Closed chest dogs were anesthetized with chloralose or pentobarbital; lidocaine was administered at varying rates for 2 hours and defibrillation threshold periodically redetermined. Similar protocols were followed for bretylium. Serum lidocaine levels from therapeutic to toxic ranges were obtained, and up to a 60% (p less than 0.05) increase in defibrillation threshold in the pentobarbital-anesthetized dogs was demonstrated. In chloralose-anesthetized dogs the lidocaine effect was modest, with only a 10 to 20% rise in defibrillation threshold (p = NS) despite similar increases in serum lidocaine levels. Thus, lidocaine increases the minimal energy requirements for transthoracic defibrillation, but this effect is in part anesthesia-related, indicating a lidocaine-pentobarbital interaction. When phentolamine was administered to chloralose-anesthetized dogs receiving lidocaine, defibrillation threshold rose 13% (p less than 0.05); this suggests that alpha-adrenergic receptor blockade is at least in part the mechanism of the pentobarbital-lidocaine interaction on defibrillation threshold. Bretylium with either anesthetic had no significant effect on defibrillation threshold.