To determine whether doses of ipratropium bromide (IB) greater than those usually administered by aerosol (75-250 micrograms) give a greater degree of protection from exercise-induced asthma (EIA) in children, 12 patients with chronic asthma, ages 7-13 yr, were challenged with methacholine and exercise after inhalation of saline or 125, 250, 500, and 750 micrograms of IB on different days. A small and similar bronchodilation (mean increase over baseline: 5.26%) was observed 60 min after the administration of each dose of IB. IB prevented the bronchoconstriction caused by methacholine in all doses we used without statistically significant differences between them. All doses gave an all-or-none protection from EIA. Mean percent fall in FEV1 after exercise was 36.8, 18.3, 23.7, 27.1, and 23.2 following inhalation of saline or 125, 250, 500, or 750 micrograms of IB, respectively. The degree of protection from EIA was not correlated with the bronchodilation caused by IB. We suggest that muscarinic mechanisms are only partly responsible for the pathogenesis of EIA in children. Their importance varies among subjects and also may be variable in the same subject. Alternative mechanisms may be responsible for bronchoconstriction.