The antioxidant enzymes copper/zinc (Cu-Zn) and manganese (Mn) superoxide dismutase (SOD) have been implicated in protection of the lungs from oxidant damage. Mn SOD in particular may be related to acquired tolerance in cells following chronic ozone exposure. In order to study these protective and adaptive phenomena in oxidant injury, the cellular location and relative abundance of Mn SOD and Cu-Zn SOD were examined in the lungs of Fischer 344 rats following exposure to 0.0 and 1.0 ppm ozone for up to 3 mo using immunolabeling and morphometric techniques. Cu-Zn SOD labeling was found to be markedly reduced following ozone exposure in epithelial cells within airways and parenchyma. In contrast, a significant increase was noted in Mn SOD labeling in the centriacinar regions of exposed lungs for both alveolar macrophages and epithelial type II cells. Mn SOD labeling per epithelial type II cell was significantly increased in alveoli 0-400 microm beyond the bronchiole-alveolar duct junction (BADJ), while type II cell Mn SOD labeling was similar to control values with greater distance down the alveolar duct. No induction of Mn SOD was noted in type I epithelial cells, fibroblasts, or Clara cells. Thus, alterations in Cu-Zn and Mn SOD are both site and cell specific in the lungs. The differential increase in Mn SOD in type II cells of the proximal alveolar duct may reflect the ability of these cells to acquire tolerance and to resist further injury to repeated ozone exposure.