We have previously shown that whole body exposure of human subjects to environmental conditions of 37 degrees C and 90% relative humidity (RH) prior to and during nasal challenge with antigen decreases the early response. In this study, we evaluated 1) whether the decreased responses observed resulted from decreased end organ sensitivity to histamine and 2) whether the effect of hot, humid air persisted after the subject exited the hot, humid environment. Ten asymptomatic seasonal allergic subjects and 11 nonallergic subjects were randomized to environmental chamber conditions of either 20 degrees C, 30% RH or 37 degrees C, 90% RH for 1 hour prior to and during performance of a nasal challenge with histamine. Twenty-two hours after exiting the environmental chamber, the allergic subjects were challenged with antigen. During both chamber conditions, histamine challenge was associated with a significant increase in all measured parameters compared to sham challenge, except for the sensations of pruritus and congestion. The response to histamine challenge was not different under the two experimental conditions or between allergic and nonallergic subjects. Following both exposure conditions, allergen challenge was associated with an increase in all measured parameters compared to sham challenge, with no significant difference between the two conditions. Exposure to 37 degrees C, 90% RH minimally affects the response to nasal challenge with histamine, and thus, the previously reported decreases in the early nasal response to antigen may primarily result from reduction in mast cell activation. The effect on antigen does not persist 22 hours after exposure.