A 64-year-old male was admitted to our hospital with complaints of the development of high fever, cough and dyspnea 5-6 hours after painting automobiles. His chest X-ray film showed interstitial shadows in both lungs. Pulmonary function test demonstrated reduction of diffusion capacity; and blood gas analysis demonstrated hypoxemia and an increase in alveolar-arterial oxygen tension difference. Marked lymphocytosis and a striking decrease in CD4/CD8 ratio were observed in the bronchoalveolar lavage fluid. Transbronchial lung biopsy specimens showed alveolitis and Masson's bodies. We suspected that the patient was suffering from hypersensitivity pneumonitis induced by isocyanates contained in the urethane paint he used. Immunological studies were performed using chemical compounds of three species of isocyanate molecules (TDI, MDI, HDI) and human serum albumin (HSA). The results were as follows: skin tests were positive for TDI-HSA and MDI-HSA; lymphocyte-stimulation tests on peripheral blood were positive for TDI-HSA; precipitation reaction was negative for all the isocyanates studies; enzyme-linked immunosorbent assay (ELISA) demonstrated the existence of specific IgG antibodies for TDI, MDI and HDI; inhalation challenge test by TDI-HSA was negative, but environmental provocation was considered to be positive. We diagnosed his pulmonary disorder as hypersensitivity pneumonitis due to isocyanates. Type III and Type IV allergic reactions of Gell-Coombs were suggested to be involved in the pathogenesis, however, there remains the possibility that the instability of isocyanate compounds as antigen modified the results of our immunological studies.