The airway epithelium is a complex physicochemical barrier that plays a pivotal role in host defense. Epithelial cells have been shown to be a rich source of several classes of modulatory compounds, of which the cytokines form the largest group and possibly play the most important role in the etiology of airway disease. Evidence suggests that there are differences in the airway epithelial cells of individuals with and without respiratory disease, both with regard to (1) their capacity to express and release different types and quantities of specific cytokines and (2) their reactivity to inhaled irritants. Consequently, it is tempting to speculate that differences in epithelial cell function are an important determinant of the predisposition to respiratory disease. However, whether the differences are a result of an intrinsic defect, an acquired property due to the disease process itself, or a combination of the two, remains to be determined. In view of advances that have been made in the understanding of the putative underlying mechanisms in airway diseases, it should be possible to formulate novel therapeutic agents in the form of specific monoclonal antibodies directed against specific proinflammatory cytokines. Mills PR, Davies RJ, Devalia JL. Airway epithelial cells, cytokines, and pollutants.