O ur purpose was to determine whether exposure to a realistic concentration of nitrogen dioxide (NO2) could increase the bronchial sensitivity of asthmatic patients to bronchoconstrictor agents. We established dose-response curves for changes in specific airway resistance (SRaw) in response to aerosolized carbachol in 20 asthmatics after each had spent 1 h in an exposure chamber breathing on one occasion unpolluted air and on a separate occasion 0.1 ppm NO2: sequence of exposures to unpolluted air and to low levels of NO2 were randomized in a single-blind fashion. NO2 induced a slight but significant increase in initial SRaw and enhanced the bronchoconstrictor effect of carbachol in 13 subjects: curves were shifted to the left and the mean dose of carbachol producing a twofold increase in initial SRaw was decreased from 0.66 mg to 0.36 mg (P less than 0.001). In contrast, NO2 neither modified the initial SRaw nor the bronchoconstrictor effect of carbachol in seven subjects. In 4 out of the 20 subjects, exposure to a higher concentration of NO2 (0.2 ppm) yielded variable results. Potentiation of the carbachol bronchoconstrictor response by NO2 could not be related to any physical or clinical characteristics of the subjects tested. Although the mechanisms underlying the NO2 effect remain controversial, the present results demonstrate that very low levels of NO2 can adversely affect some asthmatics.