The effects of pretreatment with 2-O-octadecylascorbic acid (CV-3611), a novel liposoluble free radical scavenger, on reperfusion-induced arrhythmias were studied in isolated perfused rat hearts (n = 15 per group). The hearts were subjected to 10 min of coronary artery occlusion and 3 min of reperfusion. Pretreatment with CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular fibrillation (VF; reversible plus sustained) from its control value of 93% to 47% (p less than 0.05). Furthermore, CV-3611 reduced the incidence of sustained VF in a dose-dependent manner, from 67% in the control group to 13% in the CV-3611, 20 mg/kg treated group (p less than 0.01). CV-3611 (5 and 20 mg/kg) reduced the incidence of ventricular tachycardia (VT) from its control value of 93% to 73%. Pretreatment with ascorbic acid (5 mg/kg) had no effect on VF and VT. The myocardial content of CV-3611 was proportional to the dosage. We concluded that CV-3611 could reduce significantly the susceptibility to reperfusion-induced arrhythmias, especially VF, and that its effect may be due to the elimination of oxygen-derived free radicals by CV-3611 present in the membrane and the capture of lipid radicals, thereby inhibiting lipid peroxidation.