To identify constituents of grain dust responsible for grain handlers' respiratory symptoms, 11 volunteer grain elevator workers underwent inhalation provocation tests with extracts of durum wheat, durum wheat airborne dust, and grain insects and mites. Factors that might influence the host response to the challenge were assessed. Five of the 11 subjects showed a greater than 20 percent decrement in FEV1 after inhalation of durum wheat extracts (airways reaction). The bronchial reactions were immediate in 1/5 and late in 4/5. These airway reactions were blocked by sodium cromoglycate. Only one subject showed airway reaction to durum wheat dust extract, and none reacted to mites or insect extracts. There was no change in DLCO, temperature, or in total C3 complement blood levels, nor was there evidence of activation of complement by the alternate or classic pathway. The airway response was not always related to the atopic status of the individual. The reaction is more likely to occur in subjects with preexisting airway obstruction and nonspecific bronchial hyperreactivity. Durum wheat has been identified as an inducer of occupational asthma in grain handlers. This reaction is probably due to specific or nonspecific mediator release. There was no apparent parenchymal or systemic reaction or complement activation detectable in the subjects' sera after inhalation of durum wheat extracts.