Antiarrhythmic drugs, such as lidocaine, quinidine, and procainamide, have been shown to be effective against postischemic reperfusion injury in isolated rat lungs. Rat lungs were perfused at a constant flow with Krebs-Henseilet buffer supplemented with 4% bovine serum albumin and ventilated with air containing 5% CO2. The lungs were subjected to ischemia by stopping perfusion and ventilation for 60 min followed by 30 min of reperfusion. Lung injury was determined by measuring the increase in wet-to-dry lung weight ratio, while pulmonary arterial pressure and peak airway pressure were calculated from the pre- and postischemic differences. Lidocaine, quinidine, and procainamide at doses of 5, 10, and 20 mg/kg body weight, respectively, were found to attenuate the postischemic lung injury significantly (p < 0.0001). The formation of cyclooxygenase products, which were elevated during reperfusion, was also significantly (p < 0.0001) inhibited by these drugs. Since these antiarrhythmic agents are found to be powerful scavengers of hydroxyl radicals and can prevent membrane lipid peroxidation, these findings suggest that the antioxidant properties of these drugs may, in part, be responsible for protecting the lungs against reperfusion injury.