Interstitial lung diseases are a heterogenous group of disorders characterized by various degrees of parenchymal alveolitis and fibrosis. Alveolar macrophages (AM) are the predominant inflammatory cell type within alveolar structures and function not only as phagocytic cells but also as secretory cells that release various secretory products involving oxygen metabolites. Alveolar macrophages from patients with interstitial lung disease are thought to participate in the injury to the alveolar wall and contribute to the development of interstitial fibrosis. To investigate the role of alveolar macrophages in interstitial lung diseases, we measured the amount of superoxide release and phagocytosis by AM after bronchoalveolar lavage (BAL) from the normal controls and cases with interstitial lung diseases. The results were summerized as follows: 1) The total number of inflammatory cells in the BAL fluids increased more in patients with interstitial lung diseases than in the controls (p<0.02). 2) The differential cell count of BAL inflammatory cells showed that lymphocytes were predominant in sarcoidosis, hypersensitivity pneumonitis, and collagen lung disease, while neutrophils were predominant in idiopathic pulmonary fibrosis and bleomycin-induced pneumonitis. 3) The superoxide release by AM in patients with interstitial lung diseases was higher than the normal controls, either spontaneously or after stimulation by phorbol myristate acetate (PMA)(p<0.05). 4) The phagocytosis of non-opsonized staphylococcus aureus by AM was elevated in the interstitial lung disease cases (p<0.02), but no difference was noted when using the opsonized staphylococcus aureus as a target. These results suggest that AM are activated in interstitial lung diseases, and increased production of oxidant by AM in interstitial lung diseases may play a critical role in tissue damage and pulmonary fibrosis. Elevation of oxygen metabolite release by AM could be a useful marker in the assessment of the activity of interstitial lung diseases.