We have prospectively evaluated 150 workers exposed to hexamethylene diisocyanate (HDI) and its trimer (THDI) during an 18-month period. The evaluation consisted of periodic serum antibody studies and a questionnaire that was designed to attempt to identify symptoms compatible with work-related syndromes of allergic rhinitis, allergic conjunctivitis, hypersensitivity pneumonitis, asthma, or irritant reactions. The study population was divided into seven groups on the basis of job classification. The groups differed in exposure levels but were similar in terms of age, sex, smoking history, and duration of work with isocyanates. IgE and IgG against HDI and THDI conjugated to human serum albumin (HSA) (HDI-HSA and THDI-HSA) were determined by ELISA. There were no instances of immunologically induced disease among the 21% of workers in this sample with antibody; however, there is insufficient evidence at this time to make judgments about the relationship between antibody and clinical disease. The antibody was generally low-level IgG that may be a sensitive indicator to detect exposure to certain reactive chemicals. The level of antibody was not different among job classes or between smokers and nonsmokers. Moreover, there was no correlation between antibody level and exposure duration in these workers whose exposure levels are all well below National Institute for Occupational Safety and Health recommendations. Further evaluation will extend these observations.