The effect of inhaled corticosteroid therapy on airway mucosal inflammation was investigated in 10 symptomatic atopic asthmatic patients treated with inhaled albuterol and whose disease severity required preventative antiinflammatory treatment. Endobronchial biopsies were obtained by fiberoptic bronchoscopy before and after 6 wk of therapy with inhaled beclomethasone dipropionate (2,000 micrograms/day for 2 wk followed by 1,000 micrograms/day for 4 wk). Following treatment, there was a significant increase in mean morning peak expiratory flow (p less than 0.05) and baseline FEV1 measured on the day of methacholine challenge (p less than 0.05) and a decrease in asthma symptoms (p less than 0.01), peak expiratory flow variation (p less than 0.05), and albuterol usage (p less than 0.05). This was accompanied by a sevenfold decrease in airway responsiveness (p = 0.001). The clinical improvement in asthma was associated with a significant (p less than 0.05) reduction in epithelial and mucosal mast cells and eosinophils and submucosal T lymphocytes, but electron microscopy did not identify any changes in the extent of mast cell and eosinophil degranulation following treatment. Because of the association between the decrease in inflammatory cell numbers and the improvement in all the measured clinical and physiologic indices of asthma, we suggest that the beneficial effect of inhaled corticosteroids in asthma may be attributed to their antiinflammatory action in the bronchial mucosa.