The possible role of oxygen free radicals in the development of reperfusion arrhythmias was investigated using a 10-min period of coronary ligation followed by reperfusion in the isolated rat heart. Superoxide dismutase (5 to 20 u/ml) glutathione (10(-5) to 10(3)M) and ascorbic acid (10(-4) to 5 X 10(-4) M) when given before coronary ligation attenuated the development of reperfusion arrhythmias. Mannitol (2 X 10(-2)M) and catalase (100 and 300 u/ml) did not have any significant effect on reperfusion arrhythmias when given alone but they did potentiate the antiarrhythmic effect of superoxide dismutase. Glutathione, and a combination of superoxide dismutase, catalase and mannitol also reduced the incidence of reperfusion induced ventricular fibrillation when given just before reperfusion. By perfusing hearts with ferricytochrome C it was possible to show an increased reduction of ferricytochrome C during the first minute of reperfusion which could be prevented by the addition of superoxide dismutase. These results provide evidence that oxygen free radicals are produced and may be important in the genesis of reperfusion induced arrhythmias in the isolated rat heart.