Background: Chemical-induced hypersensitivity pneumonitis has been so far rarely described. The purpose of this study was to find out whether hypersensitivity pneumonitis is a common disorder in isocyanate workers. Methods: Company physicians' case histories of 1780 isocyanate workers were evaluated. In 16 subjects suspected of having isocyanate-induced hypersensitivity pneumonitis, chest x-ray films were made; levels of IgE and IgG antibodies to isocyanate–human serum albumin were estimated; conjugates and isocyanate challenge tests, bronchoalveolar lavage fluid analyses, and/or lung histologic investigations were performed. Results: Each of the 14 study patients who had hypersensitivity pneumonitis had work-related dyspnea and fever occurring several hours after the start of work with isocyanates. Typical clinical findings were the reduction of lung diffusing capacity (n = 10), reticular or nodular lung patterns in the x-ray film (n = 9), and serum IgG antibodies specific to isocyanate–human serum albumin conjugates (n = 10). Restrictive ventilation patterns in the inhalation challenge tests (n = 5), lymphocytic and/or neutrophilic alveolitis seen in bronchoalveolar lavage fluid analyses (n = 7), and lymphohistocytic patterns mostly associated with mild fibrosis in lung histology (n = 5) confirmed the diagnosis. Conclusion: Occupational exposure to isocyanate vapors and aerosols induces typical hypersensitivity pneumonitis in at least 1% of the isocyanate workers with symptoms. Diphenylmethan diisocyanate was found to be the main cause of this disorder. (J ALLERGY CLIN IMMUNOL 1995;95:1004-10.)