To determine whether oxygen radical scavengers inhibit ozone-induced airway hyperresponsiveness, we examined the protective effect of polyethylene glycol-superoxide dismutase (PEG-SOD) and PEG-catalase (PEG-CAT) on ozone-induced airway hyperresponsiveness in cat airways. Twenty-five cats divided into five groups were anesthetized and mechanically ventilated. There was no difference between the groups in baseline airway responsiveness to inhaled acetylcholine (ACh). In the control group, AChPC, the concentration required to produce a doubling increase in baseline pulmonary resistance, was significantly reduced by ozone exposure (2.0 ppm for 2 h); the ratios of AChPC before ozone exposure to after ozone exposure (AChPC ratio) were 14.8 +/- 5.7 (p < 0.001) and 4.80 +/- 1.6 (p < 0.01) 30 and 120 min after exposure, respectively. Local administration of PEG-SOD (2,000 U/kg) into airways partially but significantly prevented ozone-induced airway hyperresponsiveness. The AChPC ratios were 6.2 +/- 1.4 and 1.5 +/- 0.2 30 and 120 min after exposure, respectively, which were significantly different from those of the control group (p < 0.05), whereas PEG-CAT pretreatment (6,000 U/kg) was without effect. Combined pretreatment with PEG-SOD and PEG-CAT had no additional protective effect compared with PEG-SOD alone. PEG-SOD had no direct effect on airway responsiveness to ACh. These results suggest that superoxide may be involved in ozone-induced airway hyperresponsiveness.