Twenty-seven workers with occupational exposure to hexahydrophthalic anhydride (HHPA) from an epoxy resin molding system were studied to evaluate the nature of their reported respiratory complaints. The workers were evaluated by questionnaire, pulmonary function tests, and serologic investigations. The presence of serum-specific IgE and IgG to an HHPA-human serum albumin (HSA) conjugate was measured by use of RAST and ELISA assays. Estimates of exposure to HHPA were made for each worker on the basis of job description and environmental sampling. Seven workers reported symptoms of asthma and rhinitis; four workers had symptoms consistent with occupational asthma. Fourteen of the remaining 20 workers reported nasal or ocular symptoms while they were at work. No worker demonstrated a significant (>20%) pre- to postshift decrement in FEV1. Twelve workers had significant levels of specific IgE to HHPA-HSA; 11 had elevated levels of specific IgG to HHPA-HSA. A group of workers estimated to have higher exposures to HHPA had a significantly higher mean total IgE level (p < 0.05) and significant titers of HHPA-HSA-specific IgE or IgG, or both (p = 0.048) as compared to a group with lower exposure to the anhydride. All four workers with occupational asthmal rhinitis had significant levels of specific IgE to HHPA-HSA (ranging from 8.7% to 23.4% RAST binding); three workers did not work directly in the HHPA area but were located in nearby sections of the plant with lower exposures to HHPA. Three workers with symptoms of asthma not clearly associated with the workplace did not have significantly elevated specific IgE levels. Another radioimmunoassay with the use of beads coated with mouse monoclonal antihuman IgE was used to quantitate the amount of specific anti-HHPA-HSA binding (range 1.0 ng to 32.6 ng/ml) present in workers' sera. The solid-phase bead radioimmunoassay was inhibited by the homologous HHPA-HSA conjugate but not by HHPA hapten alone in two workers, suggesting that these workers were sensitized to new antigenic determinants. We conclude that HHPA is a potent industrial sensitizer and is capable of inducing IgE-mediated disease. Prospective investigations are required to define the incidence and severity of clinical sensitivity.