Diisocyanates, highly reactive chemicals used in the production of polyurethanes, are currently the most frequently reported cause of chemically induced occupational asthma and their use continues to rise. The prevalence of diisocyanate asthma among exposed workers is estimated to range from 5% to 15%. Routes of exposure include the respiratory tract and skin. Workplace exposures are difficult to quantify and control, and there is no simple diagnostic test for the disease. This review considers recent concepts in exposure. clinical aspects and pathogenesis of the disease. The pathogenesis of diisocyanate asthma remains unclear, with evidence supporting both immunological and nonimmunological mechanisms. Knowledge of the chemical reactivity of diisocyanates, the target biomolecules, and the cellular sites of reaction are fundamental to understanding diisocyanate toxicity and disease. Recent findings of chemical interactions with biological nucleophiles will be described. The importance of diisocyanate-adducted biomolecules will be emphasized and their potential contributions to pathogenesis discussed. It is anticipated that greater understanding of the immunopathogenesis of diisocyanate asthma, including the initial cell/diisocyanate reactions, should lead to clinically useful markers of exposure and early disease.