1. The efficacy of magnesium sulfate for prevention of ventricular fibrillation was compared with that of the calcium blocker verapamil and other antiarrhythmic drugs in 54 open-chested anesthetized dogs during a 3-h ligation of the circumflex coronary artery. Latency time to fibrillation, incidence of fibrillation and hemodynamic parameters were assessed. 2. Ventricular fibrillation occurred in 11 of 14 (79%) control dogs, in 2 of 8 (25%) dogs treated with magnesium sulfate (100 mg/kg) and in none of 8 animals treated with verapamil (0.2 mg/kg) (P = 0.014 and P = 0.0004, respectively, in comparison with controls); lidocaine (60 mg followed by 4 mg/min), amiodarone (5 mg/kg) and propafenone (4 mg/kg) had no effect on the incidence of fibrillation. 3. The latency time to fibrillation was 11.6 +/- 9.1 min in controls and it was shortened to 4.0 +/- 3.8 min (P = 0.039) in dogs treated with propafenone, but was unaffected by other drugs. 4. There was no correlation between pre-occlusion heart rate or blood pressure and fibrillation incidence. 5. In this experimental model, magnesium sulfate infusion had a protective effect against ventricular fibrillation that was similar to verapamil, suggesting that magnesium sulfate may be useful as an antifibrillatory agent during acute ischemia.