Halothane, enflurane, and isoflurane were evaluated for antifibrillatory efficacy and compared with lidocaine, propranolol, procainamide, and verapamil in a canine acute left anterior descending (LAD) coronary artery occlusion/reperfusion model with basal pentobarbital anesthesia. Of the antiarrhythmic drugs, only verapamil prevented ventricular fibrillation during occlusion and reperfusion. Halothane 1% inspired after 15 min showed similar protection. Enflurane 2.5% inspired after 15 min resulted in significant protection but caused hypotension after occlusion in 4 of 17 dogs. Isoflurane 1.7% inspired after 15 min showed intermediate results. At inspired concentrations of 0.5% and 1.25%, respectively, halothane and enflurane protected against ventricular fibrillation without hypotension. It is concluded that the volatile anesthetics have antifibrillatory effects in this canine model but differ in their ability to cause hypotension in the presence of proximal LAD coronary artery occlusion.