As an inflammatory disorder of the respiratory system, asthma is characterized by bronchial hyper-responsiveness that appears to involve alterations of the bronchial epithelium. The existence of epithelial beta-receptors is of particular importance to respiratory function, and epithelial dysfunction in asthma may impair beta-adrenoceptor function and lead to bronchial hyper-responsiveness. After reviewing the structure and function of the respiratory epithelium and the role of epithelial beta-adrenoceptors, an in vitro model allowing the detailed study of the regulation of airway smooth muscle by epithelial cells is described. Studies with this model have demonstrated that epithelial beta-adrenoceptors participate in modulating the tone of bronchial smooth muscle cells. Activation of these beta-adrenoceptors leads to bronchial myorelaxation, probably mediated by one or more inhibitory substances generated within the epithelium. In addition, beta-adrenoceptor activity may affect smooth muscle tone indirectly by regulating mucociliary clearance and the paracellular exchange of inflammatory mediators. Since some respiratory diseases seem to be associated with beta-adrenoceptor dysfunction, therapy with beta-agonists may be beneficial by acting on beta-adrenoceptors located both on smooth muscle cells and on epithelial cells.