OBJECTIVES: This study clarified the exposure-response relationships for the organic acid anhydrides (OAA) hexahydrophthalic (HHPA) and methylhexahydrophthalic (MHHPA) anhydrides and the development of specific immunoglobulin (IG) E and G antibodies and work-related symptoms. METHODS: In an epoxy resin-using factory, air levels of OAA were determined by gas chromatography-mass spectrometry. Occupational, smoking, and medical histories (questionnaire) were obtained for 154 exposed workers and 57 referents. Work-related symptoms of the eyes and airways were recorded, and OAA metabolites were analyzed in urine. A skin-prick test with common allergens and conjugates of OAA were performed. Specific IgE (radioallergosorbent test) and IgG (enzyme-linked immumosorbent assay) antibodies were determined in serum, and spirometry was performed. RESULTS: Air levels of the OAA were low (HHPA <1 to 94, MHHPA <3 to 77 µg/m) and associated with the concentrations of the OAA metabolites in urine. Furthermore, for the exposed workers, there were high prevalences of sensitization (IgE 22%, IgG 21%), which correlated with the exposure. Neither atopy nor smoking increased this risk significantly. Furthermore, work-related symptoms were more prevalent among the exposed workers than among the referents (eyes 23% versus 14%, nose 28% versus 16%, nose bleeding 8% versus 0%, lower airways 10% versus 4%), and they were related to the exposure [adjusted prevalence odds ratios (POR) in the highest group 7.7, 3.6 and 17, respectively) and the IgE levels (POR 4.9, 3.1 and 5.6, respectively). CONCLUSIONS: In spite of the very low OAA levels in the air and metabolites in the urine, there were high and exposure-related risks of specific IgE and IgG sensitization and of work-related symptoms for the eyes, nose (especially bleeding), and lower airways.