To investigate whether exercise increases the responsivity of the tracheobronchial tree to nonspecific stimuli, 11 atopic asthmatics underwent serial challenges with aerosolized methacholine before and 4 and 24 h after an asthma attack induced by cycle ergometry while breathing cold air (mean +/- SE = -11 +/- 1 degree C). Bronchodilator therapy was withheld the day before and throughout each study day. There were no significant differences in base-line lung function before exercise or any of the three methacholine bronchoprovocations. Exercise produced a 25 +/- 3% maximal fall in 1-s forced expiratory volume (FEV1) within 15 min. This attack was not associated with either an immediate or a delayed increase in methacholine sensitivity. The provocation concentration of methacholine required to reduce the FEV1 20% from saline control at base line and 4 and 24 h after exercise were 0.8 +/- 0.5, 0.9 +/- 0.5, and 1.1 +/- 0.8 mg/ml, respectively. This was not significant by a one-way analysis of variance (F = 0.078, P = NS). These data demonstrate that exercise-induced asthma does not produce an increase in nonspecific bronchial reactivity. Hence, if mediators are elaborated with exercise as has been suggested, they appear to function differently than when released by antigen.