ABSTRAfl. Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type I1 cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type I1 cells compared with adults. Baseline enzyme activities did not differ in neonatal type I1 cells and lung homogenates except for lower catalase activity in type I1 cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type I1 cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type I1 cells there was a significant decrease in SOD activity after 0 2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type I1 cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type I1 cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type 11 cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate. 4in cellular protective mechanisms, such as the antioxidant enzyme system, which includes the enzymes GPX, CAT, and SOD (5). It is known that the neonatal animal responds to exposure to >95% 0 2 with increased activities of antioxidant enzymes in the lung, an enzyme response not observed in the adult lung (2-4).The particular cell types that may be responsible for increases in antioxidant enzyme activity in the neonate have not been identified. Previous investigations of adult type I1 cells have produced conflicting data on whether antioxidant enzyme activities are higher in type I1 cells than in whole lung and whether antioxidant enzyme activities in type I1 cells increase after hyperoxia (6, 7). One previous investigation of neonatal type I1 cells has suggested that antioxidant enzyme activities do not increase in this cell type after hyperoxia (8). However, because the type I1 cell is relatively resistant to oxygen damage compared with other cell types and appears to be important for proliferation and repair of the pulmonary epithelial lining after damage (5, 9), we hypothesized that this cell might play a role in neonatal tolerance. This study was designed to test the hypotheses that 1) baseline (air-exposed) antioxidant enzyme activities would be higher in neonatal type I1 cells than in whole lung and 2) the activities of the antioxidant enzymes in neonatal type I1 cells would rise to a greater extent in...