We investigated whether airway responsiveness to methacholine differs in subjects with a history of sensitization to TDI who develop immediate, dual, late, or no asthmatic reactions after exposure to TDI, and also the effect of a TDI inhalation challenge in asthmatic subjects with hyperreactive airways with no history of sensitization to TDI. We measured FEV-1 immediately before and after exposure to TDI (0.018 ppm; 5-30 min) and then hourly for 8 h and the provocative dose (mg) of methacholine that caused a decrease in FEV-1 of 20% (PD20 FEV-1). The results of the present study suggest that the bronchoconstrictor effect of isocyanates is specifically linked to exposure to TDI and subsequent sensitization, excluding a nonspecific irritant effect on the airways. Moreover, they suggest that the increase in airway responsiveness to methacholine associated with the late asthmatic reaction is linked to factors that cause the late component of the asthmatic reaction.