Nine asthmatic patients with a mean age of 14 yr received bronchial challenges with histamine and methacholine. The challenges were repeated after inhalation of 80 microgram of SCH 1000 (ipratropium bromide) and 5 mg of chlorpheniramine maleate. The provocation doses which produced a 20% fall in forced expiratory volume in 1 sec (FEV1) and the slopes of the dose-response curves were analyzed. SCH 1000 prevented methacholine-induced bronchoconstriction and chlorpheniramine prevented methacholine-induced bronchoconstriction. There was no significant change in the dose-response curve of histamine after SCH 1000 or in the dose-response curve of methacholine after chlorpheniramine. The findings indicate that the mechanisms and receptor sites involved in bronchial provocation by histamine and methacholine are distinctly different. The histamine response is unlikely to be vagally mediated because histamine-induced bronchoconstriction was not prevented by SCH 1000. Both SCH 1000 and chlorpheniramine caused significant bronchodilatation, suggesting the presence of both histamine- and vagal-dependent bronchomotor tone.