To study the relative contributions of parasympathetic and sympathetic mechanisms in airway obstruction in patients with emphysema, we gave supramaximal doses of anticholinergic and adrenergic agents in sequence and in combination. Serial doses of one agent were administered to achieve a plateau of bronchodilatation; after that the other agent was administered. The plateau achieved with the anticholinergic agent (atropine methonitrate) was significantly higher than that achieved with the adrenergic agent (salbutamol). When the adrenergic agent was given first, additional bronchodilatation was achieved with subsequent use of the anticholinergic agent. When the anticholinergic agent was given first, no additional bronchodilatation was achieved with subsequent administration of the adrenergic agent. When both agents were given simultaneously, the degree of bronchodilatation was virtually identical to that obtained with the anticholinergic agent alone. Tests sensitive to small-airway and large-airway function and lung volumes gave essentially the same results. Thus, all achievable bronchodilatation was obtained with the anticholinergic agent alone. These results suggest that the two classes of agents produce bronchodilatation through a common cholinergic pathway in emphysema, and support the concept that parasympathetic activity is the dominant reversible component of airway obstruction in this disease.