To determine the efficacy of left ventricular drainage in permitting defibrillation after prolonged, refractory ventricular fibrillation, 12 dogs (7 normal, 5 with major coronary arterial ligation) with 21 episodes of either spontaneous or electrically induced ventricular fibrillation were studied before and during left ventricular drainage by means of transaortic or transatrial cannulation. After prolonged ventricular fibrillation without circulatory support (average 28, range 17 to 48 minutes), electrical defibrillation was unsuccessful despite increasing amounts of direct current. Defibrillation was then attempted during graded amounts of left ventricular drainage (200 to 1,800 ml/min; 8.7 to 57.6 ml/kg per min). Defibrillation was successful in each instance (10 watt-sec), at an average left ventricular drainage flow rate of 19.7 ml/kg per min (range, 12.1 to 30.4). Successful defibrillation was obtained with either low or normal arterial pH values. Left ventricular drainage with concomitant successful defibrillation was associated with significant increments of arterial PO2. Submaximal volumes of left ventricular drainage may permit defibrillation after prolonged refractory ventricular fibrillation, both in normal animals and in those with acute myocardial infarction. Acute reduction of left ventricular volume with alteration of the form of the left ventricle, reduction of myocardial oxygen requirement and increments of coronary flow attributable to left ventricular drainage are postulated as mechanisms facilitating defibrillation. It is suggested that application of left ventricular drainage through a closed chest may be helpful in certain clinical instances of refractory ventricular fibrillation.