Our study was designed to assess the role of selenium (Se) in development of neonatal lungs under conditions of normoxia and hyperoxia. Thirty-six female Sprague Dawley rats were bred and fed a Se-deficient (0.03 ppm Se) or a Se-adequate (0.5 ppm Se) diet during pregnancy and lactation. At d 2 postpartum, 24 litters were randomly assigned to either high oxygen (greater than 95%) or air and were cross-fostered for 4 d. Lung weight was significantly enhanced in Se-adequate pups and was not related to high oxygen or air exposure of either the pups or dams. Two types of histologic lesions were observed in the lungs of the pups: septal attenuation and interstitial inflammation. When reared in oxygen, all (17 of 17) Se-deficient pups had lesions. In contrast, only 60% (9 of 15) of Se-adequate pups were affected (p less than 0.01). Lung lesions also were more severe in Se-deficient pups. Se-deficient pups also displayed a significant degree of septal attenuation when reared in air. Se-dependent glutathione peroxidase activity in the pup lung was significantly elevated in response to hyperoxia and was unrelated to Se nutriture. No differences in activities of lung superoxide dismutase, catalase, and glutathione s-transferase were noted between Se-deficient and Se-adequate pups reared in air or high oxygen environments. These data indicate that Se has an important role in the development of neonatal lungs, a role that is even more pronounced during conditions of hyperoxia. The protective role of Se in developing lung tissue cannot be completely explained by enhanced glutathione peroxidase activity.