Allergen-induced late asthmatic responses are associated with an increase in bronchial responsiveness to histamine. We have examined the relationship between the magnitude of the late asthmatic response and the magnitude and duration of increased histamine responsiveness. Allergen inhalation tests were carried out in 12 asthmatic subjects to induce a mild early asthmatic response (16% to 40% reduction in FEV1 in the first hour after allergen inhalation); the response was followed over 8 hr to identify the occurrence and magnitude of any late asthmatic response (maximum fall in FEV1 from baseline between 3 and 8 hr). The provocation concentration of histamine causing a decrease in FEV1 of 20% (PC20) was measured before and after inhalation of allergen. The magnitude of decrease in PC20 correlated with the magnitude of the late asthmatic response as measured by the percent fall in FEV1 (r = 0.8, p < 0.002). The duration of decrease in PC20 was from 2 to 74 days and this also correlated with the magnitude of the late response (r = 0.53, p < 0.05). Total lung capacity (TLC), residual volume (RV), FEV1, maximal expiratory flow-volume curves (on air and He-O2), and histamine responsiveness were also measured before and at intervals after allergen inhalation. Four of seven subjects still had a reduction in PC20 when the TLC, RV, FEV1, maximal expiratory flow-volume rates on air (V̇50air) and He-O2 (V̇50He-O2) (measured at an absolute volume corresponding plus 50% of control vital capacity) and ratio of V̇50He-O2 to V̇50air were back t preallergen inhalation levels. In two of these subjects volume of isoflow was also back to ±10% of preallergen inhalation levels when the PC20 was still significantly reduced. The results suggest that allergen-induced late asthmatic responses can be associated with an increase in bronchial responsiveness to histamine by mechanisms other than a reduction in baseline airway caliber alone.