The airway epithelium controls the chemical and physical properties of airway surface fluid and consequently mucociliary clearance. The treatment for 24-48 hours of human bronchial epithelial cells with interferon-gamma or interleukin-4 leads to marked changes in transepithelial ion transport properties. Both cytokines downregulate the activity of the epithelial Na+ channel and, at the same time, upregulate Ca2+-dependent Cl- secretion. Interleukin-4 also increases the expression and function of the cystic fibrosis transmembrane conductance regulator Cl- channel. These results suggest that some inflammatory stimuli may change the balance between fluid absorption and secretion to favor hydration of the airway surface and consequently mucus clearance.