Usual interstitial pneumonitis (UIP) is an idiopathic inflammatory disorder that produces scarring of the lung parenchyma. We studied open-lung biopsies of 13 patients with UIP using immunohistological staining and monoclonal antibodies. T lymphocytes (Leu 4+) accounted for 59% of cells in the alveolar septal infiltrates in UIP and OKT8+ cells accounted for the majority of T lymphocytes in most cases. OKM1+ granulocytes comprised a smaller percentage (14%) of the alveolar infiltrates. Granulocytes were most frequent within cystic airspaces and inflamed small airways. Class II HLA (Ia) antigens were expressed on lymphocytes, macrophages, endothelial cells, and alveolar type II cells in lungs with UIP. This study demonstrates that altered immunoregulatory subsets are present in the lungs of patients with UIP and suggests the possibility that activated T cells may play a role in the pathogenesis of this disorder.