A worker developed two episodes of severe asthma 90 min after cut ting a polyurethane plate made of diphenylmethane diisocyanate (MDI) using a rapidly turning carbide blade. Intradermal skin testing with MDI-human serum albumin (MDI-HSA) and p-tolyl isocyanate-HSA (p-TMI-HSA) were positive at 0.002 mg/ml. Control subjects showed no reaction at 2 mg/ml. Bronchial provocations of the worker with MDI-HSA and p-TMI-HSA, made 1 year after the occupational asthmatic episode, were negative at 10 mg/ml. Bronchial reactivity to methacholine decreased toward normal during a 2-year follow-up. RAST using MDI-HSA or p-TM I-HSA were strongly positive when compared with binding by sera from atopic controls which contained the same amount of total IgE. RAST titres decreased during a 1-year follow-up. In the MDI-HSA RAST, inhibition studies indicated specificity of antibodies for MDI-HSA. In the p-TMI-HSA RAST. p-TMI-HSA was a very effective inhibitor whereas MDI-HSA was not. These results indicated the formation of at least two distinct groups of IgE antibodies: those reactive with MDI. and those reactive with p J-TMI determinants. Guinea pigs immunized with MDI formed antibodies with specificities similar to those of the patient. We conclude that the worker had occupational asthma accompanied by the formation of specific IgE antibodies of the specificities. The causal relationship of the antibodies to the occupational asthma remains uncertain.