The pathophysiological mechanisms of organic diisocyanate-induced respiratory disease remain largely unknown. Some 20% of patients have specific antibodies towards diisocyanate monomers whereas even in this circumstance their presence does not correlate very well with results in clinical provocation tests. The formation of diisocyanate haptens is the trigger for the immunological reactions. However, it is known that the reactions with protein and other macromolecules may be slow and hydrolysis of the isocyanate moities to corresponding amines as catalyzed by bicarbonate is more rapid. The liberated amines, or their intermediates, probably have an important role in the activation of tissue thromboplastin activator, loss of serum antitrypsin activity, and, finally, in neurogenic inflammation. Hypothetically, susceptible individuals probably include those which are slow acetylators of exogenous amines and carries of heterozygous antitrypsin phenotypes.