In human subjects 15-min exposure to 0.5-1.0 ppm chlorine gas causes a nasal obstructive response in the absence of a marked sensation of irritation. The current investigation was designed to assess the response of the mouse for comparative purposes. Respiratory physiological responses were measured in female C57Bl/6J mice exposed to 0.8 to 4.0 ppm chlorine gas. Chlorine was a potent sensory irritant with an RD50 of 2.3 ppm. The gas produced airway obstruction as indicated by a concentration-dependent increase in specific airways resistance (sRaw) during the 15-min exposure. At 0.8 ppm, chlorine produced only mild sensory irritation (<20% change in breathing frequency) and a 65% increase in sRaw. Pretreatment with atropine was without effect on the obstructive response, suggesting a lack of involvement of muscarinic cholinergic pathways. Pretreatment with the sensory nerve toxin, capsaicin, dramatically reduced both the sensory irritation and obstructive responses to chlorine, suggesting the involvement of sensory nerves. Studies were also performed using the surgically isolated upper respiratory tract of the anesthetized mouse. Chlorine was efficiently scrubbed from the airstream (>97%) in that site and produced an obstructive response that was of sufficient magnitude to account for the entire response observed in the intact animal. In summary, chlorine gas produces an immediate nasal obstructive response in the mouse that appears to be similar to that in the human.