Using radiolabeled, monodispersed aerosols (99mTc-iron oxide) and gamma camera analysis, we measured the efficacy of cough for clearing mucus from the airways of the lung following inhalation of the bronchodilator ipratropium bromide (IB) (Atrovent, Boehringer Ingelheim, Inc), a drug that has been shown to have no effect on mucociliary clearance in COPD. Clearance of radiolabeled aerosol was studied over a 2.5-h period on three separate days, a control day with no coughing, and two study days during which the patient performed controlled cough maneuvers over the course of clearance measurements following IB or placebo therapy (double blind, crossover). Fifteen patients, age > 45 years, with stable moderate-to-severe airway obstruction (mean FEV1/FVC = 0.45) were studied. IB diminished the effectiveness of cough for clearing the radiolabeled particles from the airways. This effect of IB on cough clearance may be due to (1) changes in the airflow dynamics induced by bronchodilation or (2) altered rheology or depth of airway secretions.