In asthmatic patients, short-term exposure to nitrogen dioxide at low concentrations has been reported to result in a nonuniform airway response to various bronchoconstrictive stimuli. We therefore investigated in 11 patients with mild and stable asthma with normal baseline airway tone the effect of 0.25 ppm nitrogen dioxide on the airway response to methacholine. On 2 separate days, the subjects inhaled either 0.25 ppm nitrogen dioxide or filtered air (sham) during 20 min of tidal breathing followed by 10 min of bicycle exercise at room temperature (mean exercise ventilation 30 L/min). Methacholine inhalation tests were performed 1 h after the end of exercise to determine the methacholine concentration necessary to increase SRaw by 100% (PC100SRaw). On a third day, a methacholine challenge was done without previous exposure (control). Mean (SEM) exercise-induced increase of SRaw was 80 (24) % after sham and 82 (25) % after nitrogen dioxide, which was not significantly different (p greater than 0.10). PC100SRaw did not differ on the 3 occasions, geometric mean values (variability of mean) being 0.41 (1.6). 0.41 (1.6), and 0.46 (1.5) mg/ml after sham, nitrogen dioxide, and control, respectively (p less than 0.10). We therefore conclude that in patients with mild and stable asthma short-term exposure to 0.25 ppm nitrogen dioxide during rest and exercise does not increase methacholine responsiveness 1 h after exposure.