Human bronchial epithelial cells were treated in vitro with interferon-γ or tumor necrosis factor-α to assess their effect on transepithelial ion transport. Short-circuit current measurements revealed that Na⁺ absorption was markedly inhibited by interferon-γ (10–1,000 U/ml). The cystic fibrosis transmembrane conductance regulator was also downregulated by interferon-γ as evident at the protein level and by the decrease in the cAMP-dependent current. On the other hand, interferon-γ caused an increase of the current elicited by apical UTP application, which is due to the activity of Ca²⁺-dependent Cl⁻channels. Tumor necrosis factor-α caused few changes in ion transport. Transepithelial fluid transport was measured in normal and cystic fibrosis cells. At rest, both types of cells showed an amiloride-sensitive fluid absorption that was inhibited by interferon-γ but not by tumor necrosis factor-α. Our results show that interferon-γ alters the transepithelial ion transport of cultured bronchial cells. This effect may change the ion composition and/or volume of periciliary fluid.