Free radicals have been suggested to play an important role in the pathogenesis of interstitial lung diseases, the most important of which are chronic interstitial pneumonias such as usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) and granulomatous lung diseases such as sarcoidosis. Because manganese superoxide dismutase (MnSOD) and catalase are two important intracellular antioxidant enzymes that probably play a central role in lung defense, the localization and intensity of these two enzymes were assessed by immunohistochemistry in biopsies of UIP (n = 9), DIP (n = 11), pulmonary sarcoidosis (n = 14), and extrinsic allergic alveolitis (n = 6). The mRNA of these enzymes in selected samples of bronchoalveolar lavage was assessed by Northern blotting. Catalase, but not MnSOD, was constitutively expressed, especially in type II pneumocytes of the healthy lung of nonsmoking individuals. In contrast, manganese SOD immunoreactivity was markedly upregulated in all of the interstitial lung diseases investigated, whereas no increased expression of catalase could be detected in any case. Both enzymes were expressed, especially in type II pneumocytes and alveolar macrophages of DIP and UIP, in the well-preserved areas of the lung, in the acute fibromyxoid lesions of UIP, and in the granulomas of sarcoidosis and extrinsic allergic alveolitis. The simultaneous expression of MnSOD and catalase in the alveolar region suggests their protective role against the progression of lung disease.