The effects of hyperoxia and superoxide dismutase (SOD) administration on endothelium-dependent relaxation induced by acetylcholine in isolated rabbit pulmonary artery (PA) preparations were examined. Relaxation responses to papaverine. and contractile responses to KCI and norepinephrine were also assessed using a bioassay technique. Prolonged hyperoxia in rabbits for 3 days produced loss of endothelium-dependent relaxation of the PA, and significant attenuation of contractile response to KCI and relaxation response to papaverine. These changes were prevented by subcutaneous SOD administration. Histological examination using light and electron microscopy revealed focal edema, destruction, and detachment of the PA endothelium in the PA strip preparations from these rabbits. Thus, it is concluded that a high concentration of oxygen exposure in rabbits for 3 days produces not only histological damage in the PA endothelium. but also causes impairment of vascular reactivity to constricting and relaxing agents. Subcutaneous SOD administration prevented oxygen-induced PA damage.