Seventeen out of thirty-three workers who have been exposed to airborne papain at their place of work regularly developed asthmatic symptoms such as shortness of breath, wheezing, coughing, sneezing, rhinorrhea and conjunctival irritation upon contact with this proteolytic enzyme. Investigations by RAST, skin test and bronchial provocation test proved IgE-mediated hypersensitivity to papain in fourteen symptomatic workers. Ten of these were in a screening investigation involving twenty-nine of the thirty-three workers; i.e. the incidence of IgE-mediated sensitization was 34.5% of this group. Bronchial provocation of as little as 0.001--0.5 mg of papain was shown to elicit immediate or dual asthmatic reactions in all eight tested workers with RAST values greater than 3 u/ml. On the other hand, inhalation of 0.5 mg of papain did not cause any remarkable change in non-exposed asthmatics. Occupation-related blood-stained nasal secretions and/or cutaneous flare reactions in all four heavily-exposed papain workers, of whom three had negative skin test and RAST results, suggest a direct effect of the proteolytically active enzyme on human tissue. There was a significant elevation (P less than 0.001) of serum trypsin inhibitory capacity in papain workers which seems to depend on the degree of exposure. No significant differences between symptomatic and asymptomatic workers in alpha 1-antitrypsin (Pi) phenotype subtypes were found.