The airway response to inhaled histamine is known to be influenced by various stimuli (e.g., infection, ozone). Temperature (T) has been shown to affect it in vitro. We studied whether T and humidity (H) modify airway response to inhaled histamine in normal subjects. Twelve normal subjects 21 to 46 yr of age (mean age, 29 yr) performed two similar histamine inhalation tests, the only difference being the conditions of the inspired air. One test was done while breathing cold dry air (mean T +/- SEM, -17.3 +/- 1.8 degrees C; relative H, 0%), and the other while breathing warm humid air (mean T +/- SEM, 33.9 +/- 0.5 degrees C; relative H, 100%). Whereas the geometric mean histamine concentration required to produce a 15% fall in FEV1 in the warm humid tests was 22.7 mg/ml, it was 11.9 mg/ml in the cold dry test (p less than 0.01). It is concluded that the T and H of inspired air modify the airway response to inhaled histamine in normal subjects.