CD40 is expressed in a variety of cell types including B cells and thymic epithelial cells. The present study examined the expression and function of CD40 in human airway epithelial cells. The results show that primary bronchial epithelial cells, the bronchial epithelial cell lines 16HBE14o-, IB3-1, and CFBE41o-, and the tracheal epithelial cell lines 9HTEo- and ΣCFTE290- expressed constitutively CD40 mRNA as determined via RT-PCR and Northern blot analysis (n=2-4). Constitutive CD40 protein expression was confirmed in 16HBE14o- and 9HTEo- via FACS (n=4). Incubation of the epithelial cell lines listed above with TNFα, IFNγ, and/or IL-1β (each at 100ng/ml) did not alter CD40 mRNA or protein expression (n=2-4). Cross-linking of CD40 expressed on 9HTEo- cells with soluble CD40L (mCD8hgp39, a generous gift from Dr. R. J. Noelle) induced a significant increase in the protein expression of IL-8 and MCP-1 (p≤0.05). In addition, CD40L in combination with TNFa and/or IL-1β (each at 1ng/ml) increased IL-8, MCP-1, and RANTES protein expression 2-13 fold (p≤0.05). These findings demonstrate that human airway epithelial cells express CD40. Moreover, these results suggest that CD40-CD40L interactions between epithelial cells and CD40L+ cells may increase epithelial expression of chemokines during an airway inflammatory response.