A certain critical mass of myocardium is believed to be necessary to initiate ventricular fibrillation. The right ventricular isolation procedure, employed clinically to confine ventricular tachyarrhythmias to the right ventricle, decreases the ventricular mass available for fibrillation by isolating the ventricles from each other. The effect of this procedure on ventricular fibrillation thresholds is unknown. Left and right ventricular fibrillation thresholds were measured before and after right ventricular isolation in 10 adult mongrel dogs utilizing a single 5 ms stimulus of increasing current strength applied to the epicardium during the vulnerable period. There were no significant differences in heart rate, aortic blood pressure, left atrial pressure, temperature, arterial blood gases or regional myocardial blood flow between the study periods. In 9 of the 10 dogs, the isolated right ventricle could not sustain ventricular fibrillation despite the utilization of stimulus strengths of up to 80 mA. In the 10th dog, the right ventricular fibrillation threshold increased 150%, from 20 to 50 mA. The left ventricular fibrillation threshold markedly increased in every dog, with an average increase from 23 ± 2 to 40 ± 4 mA (p < 0.0005). To determine whether time, cardiopulmonary bypass or the right ventricular incision could cause similar changes in ventricular fibrillation threshold, five different dogs underwent the entire experimental protocol except for incomplete isolation of the right ventricle. There were no significant changes in ventricular fibrillation thresholds in these dogs. Thus, in the canine model, right ventricular isolation can prevent the occurrence of sustained fibrillation in the isolated right ventricle and can significantly increase the left ventricular fibrillation threshold.