To determine the site in the parasympathetic pathway responsible for the increased bronchial reactivity in 5 atopic subjects, we studied the effect of premedication with aerosols of hexamethonium, a ganglionic blocking agent, and atropine, a postganglionic blocking agent, on the bronchomotor responses to histamine and methacholine aerosols. After 7 mg of aerosolized atropine, baseline specific airway resistance (SRaw) decreased, and the increases in SRaw produced by histamine and by methacholine were prevented in each subject (p < 0.001). After 1 g of hexamethonium, baseline SRaw was decreased to a similar level, and the increase in SRaw produced by histamine was again Prevented in each subject (P < 0.001); However, the increase in SRaw produced by methacholine was not affected significantly in 3 subjects (p > 0.5) and was increased or decreased only slightly in 2 subjects (p < 0.05). These results suggest that bronchial hyperreactivity in atopic subjects may be due to a change in the characteristics of the efferent parasympathetic pathway at a site distal to the ganglion, possibly at the smooth muscle, and that bronchodilation caused by atropine and hexamethonium cannot, by itself, account for their effects on bronchomotor responses.