The mechanism by which prostacyclin acts to prevent in vivo reperfusion injury is still uncertain. This study was therefore undertaken to assess the effect of a stable prostacyclin analogue (OP 41483-alpha-CD [OP]) on oxygen-derived free radicals after heart-lung transplantation. OP was administered to the heart-lung graft through the pulmonary artery for 25 minutes encompassing the reperfusion process. Free radicals were directly measured by electron spin resonance spectroscopy. The radical intensities of pulmonary venous blood were significantly lower in the OP group than in the control group, suggesting that fewer free radicals were generated in the lungs of the OP group. The cardiac and respiratory function were better in the OP group than in the control group. The lung is the primary source of oxygen free radical attack, and the beneficial action of OP on free radical generation is almost exclusively restricted to the lung and does not apply to the heart. This result suggested that OP probably is effective in inhibiting free radical generation from the endothelium.