An animal model of hypersensitivity pneumonitis (HP) was developed in C57Black/6J mice by repeated intratracheal inoculations with particulate Trichosporon cutaneum, a causative agent of Japanese summer-type HP. We observed severe alveolitis and bronchiolitis with infiltration of lymphocytes, macrophages, and neutrophils in the lung lesions. Granuloma formation was occasionally seen. Bronchoalveolar lavage (BAL) of the experimental animals showed an increase in the number of lymphocytes, macrophages, neutrophils, and in the total cell yield. Phenotypic analysis of the BAL lymphocytes by flow cytometry revealed that 43.1 +/- 3.1% of lymphocytes were Thy1.2+ (CD3+) cells and that the L3T4+ (CD4+) cells (36.3 +/- 3.5%) predominated over the Lyt2+ (CD8+) cells (18.5 +/- 1.2%). As for the humoral immune response, the specific IgA antibody activities in the BAL fluids well reflected the specific pulmonary inflammatory responses. Studies of lymphocyte depletion were performed by in vivo administration of anti-CD4 and anti-CD8 monoclonal antibodies. Depletions of CD4+ cells and of both CD4+ and CD8+ cells diminished the pulmonary lesions and specific IgA antibody activities in the BAL fluids. These results indicate that CD4+ cells may play a major role in the inflammatory process of this animal model.