The role of a critical myocardial mass required to maintain ventricular fibrillation initiated by rapid ventricular pacing was studied by two methods in dogs placed on total cardiopulmonary bypass. In the first method, depolarization of a limited myocardial mass was accomplished by injecting potassium chloride into one or two coronary arteries. Injection of potassium chloride simultaneously into the left circumflex and left anterior descending coronary arteries abolished ventricular fibrillation more often than did injection into any other single or combination of two coronary arteries (P < 0.0001). Ventricular fibrillation could not be reinitiated as long as the left ventricle remained inexcitable. Immersing the heart in a solution of potassium chloride or injecting the solution into the right and left ventricular cavities failed to terminate ventricular fibrillation. The second method evaluated the amount of current necessary to terminate ventricular fibrillation when the current was passed between two right ventricular electrodes, between two left ventricular electrodes and between one right ventricular and one left ventricular electrode. Electrical shocks of equal magnitude terminated ventricular fibrillation most often when those shocks were delivered between an electrode located at the right ventricular apex and an electrode located at the posterior base of the left ventricle, and least often when the shock was delivered between two right ventricular electrodes. Successful defibrillation results when a critical amount of myocardium becomes depolarized by either potassium chloride or electrical discharge; depolarization of every cell in both ventricles is not necessary to terminate ventricular fibrillation in the entire heart.