Although chlorine gas is a common irritant exposure, little is known about airway responses to chlorine inhalation among persons with baseline airway hyper-reactivity. We wished to determine whether such persons manifest an exaggerated response to chlorine compared with normal subjects. We studied 10 subjects, five with and five without airway hyperresponsiveness (HR) after exposure to 1.0 ppm chlorine and five persons, all with HR, to 0.4 ppm chlorine. After 1.0 ppm inhalation, there was a significant (p<0.05) fall (mean±SE) in FEV1 immediately following exposure among normal (−180±37 mL) and HR subjects (−520±171 mL). The fall was greater among the HR compared with the normal subjects (p=0.04). Specific airway resistance (Sraw) increased to a greater degree among the HR group compared with normal subjects (p=0.04). Among all subjects (n=10), the proportional change in FEV1 after 1.0 ppm chlorine correlated with baseline reactivity (Spearman rank correlation r=0.64, p<0.05). At 24-h follow-up, there were no significant chlorine-related pulmonary function deficits. After 0.4 ppm chlorine inhalation, there was no significant pulmonary function effect. These data indicate that persons with hyperreactive airways manifest an exaggerated airway response to chlorine at 1.0 ppm. This suggests that when large numbers of persons are exposed to chlorine, a susceptible subpopulation may acutely respond with a greater decrement in pulmonary function.