We have examined the effects of repeated exposure to antigen on airway responses to cholinergic stimulation in two inbred strains of mice that are similar in underlying cholinergic airway responsiveness, yet differ in their ability to produce IgE. Both BALB/c and SJL/J mice were repeatedly exposed to ovalbumin by inhalation for a 10-d period. While the BALB/c mice developed IgE antibody to this allergen, the SJL/J strain failed to mount an appreciable IgE response. In vitro assessments of the response of tracheal smooth muscle from saline exposed mice (controls) of both strains demonstrated responses to both methacholine and electrical field stimulation that were not significantly different between the strains. Following exposure to ovalbumin, the BALB/c strain developed a significant increase in their response to electrical field stimulation, while their response to methacholine was unaltered. In contrast, the in vitro responsiveness to these stimuli did not increase in SJL/J mice following similar exposure to inhaled nebulized ovalbumin. The passive transfer of cells from the peribronchial lymph nodes of ovalbumin-sensitized BALB/c mice into syngeneic nonimmune mice also led to increases in responsiveness of tracheal smooth muscle to electrical field stimulation. In contrast, transfer of cells from nonsensitized mice did not alter responsiveness. These results suggest that murine species capable of developing an IgE response to allergen also develop alterations in the neural control of their airways. Further, this alteration appears to be lymphocyte dependent, in that cells found within peribronchial lymph nodes following allergen exposure are capable of transferring this increase in responsiveness to nonimmune mice.