Serum IgG and IgE to isocyanate haptenized human serum albumin (HSA) were estimated by ELISA in 55 isocyanate workers who underwent isocyanate inhalation challenge studies in Montreal, Canada. The challenges were negative in 29 workers and positive in 26 workers. Isocyanate antibodies were estimated by ELISA index. The mean IgG indices were found to be significantly higher in the challenge-positive workers, and there was a similar trend for the IgE indices. Antibody specificities for toluene diisocyanate-HSA, diphenylmethane diisocyanate-HSA, and hexamethylene diisocyanate-HSA were determined by inhibition studies with a variety of isocyanate haptenized carriers. The other isocyanate substituted carriers were either noninhibitory or caused only partial inhibition as contrasted with the complete inhibition achieved by HSA conjugated to the isocyanate to which the worker was exposed. We interpret these specificity studies as indicating that the inhalation of isocyanates results in production of antibody that recognizes new antigenic determinants that develop from the coupling of isocyanates to homologous proteins.