The purpose of this study was to examine the effects of ablation of the superficial endocardium and Purkinje network on left ventricular fibrillation threshold. Lugol's solution was applied through small ventriculotomies to the left and right ventricular endocardium of 10 dogs on cardiopulmonary bypass. Two control groups of five animals each underwent either indocardial application of saline or epicardial application of Lugol's solution. Ventricular fibrillation threshold was measured before and after each intervention by the single-stimulus technique. Application of Lugol's solution to the endocardium resulted in a 102 ± 15% increase in ventricular fibrillation threshold from a control value of 26 ± 2 to 53 ± 6 mA (p<.005). In two animals, ventricular fibrillation could not be initiated postoperatively. In the control groups, there were no significant changes in ventricular fibrillation threshold. Histologic examination revealed that Lugol's solution obliterated less than 0.5 mm of superficial endocardium while sparing the adjacent myocardium. Electrophysiologic and rheologic data confirmed the discrete nature of the chemical injury. Thus ablation of the superficial ventricular endocardium with Lugol's solution results in a profound increase in the ventricular fibrillation threshold with only minimal tissue destruction.