To determine if endogenous adrenergic activity could modify the obstructive response to exercise in subjects with asthma, we had 10 subjects undergo two bouts of cycle ergometry under controlled inspired air conditions while peak expiratory flow rates and plasma catecholamines were serially recorded. The second challenge of each pair was timed to coincide with the height of the bronchospasm induced by the first. A similar protocol was undertaken with isocapnic hyperventilation to serve as a control. The initial exercise produced bronchodilatation followed by bronchoconstriction when exercise ceased. During the second challenge, the obstruction resolved totally, only to recur once more when the subjects stopped work. Plasma concentrations of norepinephrine exactly mirrored the fluctuations in pulmonary mechanics, rising with bronchodilatation and falling with bronchoconstriction. The pattern with hyperventilation differed from exercise in that there was no significant increase in norepinephrine during the challenges. To determine if norepinephrine could abolish the bronchial narrowing produced by exercise, and, as a result, possibly account for the changes in mechanics that we observed, we performed a second study in which eight subjects were administered an aerosol of this compound to inhale during an episode of exercise-induced asthma. As with the endogenous elevation, exogenously administered norepinephrine also totally abolished the attack. These data demonstrate that the sympathoadrenal activity that occurs with repetitive exercise in subjects with asthma can materially influence the severity of exercise-induced asthma.