A 68-year-old male developed dry cough and exertional dyspnea after handling paint spray containing isocyanates (TDI, MDI) for three months. Initially, the symptoms fluctuated according to whether he was at work or not. He was admitted to our hospital on February 7, 1990, because of progressive worsening of symptoms. In spite of admission to hospital and cessation of exposure to isocyanates, there was no improvement of symptoms. His chest X-ray film showed diffuse small nodular and reticular shadows. Transbronchial lung biopsy revealed thickening of the alveolar walls and formation of Masson's bodies associated with mononuclear cell infiltration in alveolar spaces. High titers of TDI-HSA and MDI-HSA specific IgG antibodies were detected by ELISA, and a high level of serum soluble IL2 receptor was also detected. From these results, we diagnosed hypersensitivity pneumonitis due to exposure to isocyanates. One week administration of prednisolone caused dramatic improvement of his symptoms, chest X-ray findings, and laboratory data. His clinical course and response to prednisolone therapy indicated that long-term steroid administration could not be avoided. The prolonged symptoms and the necessity for long-term steroid therapy are discussed.