A rare combination of an acute asthmatic reaction followed by hypersensitivity pneumonitis after exposure to diphenylmethane diisocyanate (MDI) is described. The patient, who was nonatopic and did not show bronchial hyperreactivity to metacholine, was occasionally engaged at the workplace in spraying a mixture of MDI and polyol to produce a polyurethane foam for use as a packing material. Challenge testing by MDI resulted first in a significant immediate bronchial obstruction indicated by decreases in specific airway conductance and forced expiratory volume at 1 s, and then in a significant decrease in vital capacity and diffusing capacity, associated with systemic reactions such as anorexia, malaise, fever, and leukocytosis three to eight hours after challenge. Challenge testing by toluene diisocyanate produced a mild systemic reaction. This finding, as well as the detection of specific IgG antibodies to various isocyanate-human serum albumin conjugates, suggests immunologic cross-reactivity between different isocyanates. Neither skin testing nor the radioallergosorbent test indicated a type I sensitization. After contact with isocyanates was terminated, the disease did not recur.