Gastroesophageal reflux is common in Cystic Fibrosis (CF) patients and increases the risk of aspirating (duodeno)-gastric contents into the lungs (1). Bile acid aspiration often occurs after lung transplantation and can result in an exaggerated bronchial inflammatory reaction. Thus, bile acids have been identified as possible markers associated with the development of chronic rejection (bronchiolitis obliterans) (1,2). Depending on the concentration present, bile acids have been shown to acutely stimulate or chronically inhibit colonic epithelial Cl- secretion (3). We have investigated, using the short-circuit current technique, the effects of the unconjugated bile acid, deoxycholic acid (DCA, 25 μM), and the conjugated bile acid tauroDCA (TDCA, 25 μM) on basal transport and carbachol (100 μM) or forskolin (10 μM)-induced ion transport in Calu-3 airway epithelial cells. Cultured monolayers of Calu-3 cells were grown in an air-liquid interface and mounted in Ussing chambers. Electrogenic transpeithelial ion transport was measured as short-circuit current (Isc). Data given as Mean ± S.E.M where n = number of experiments performed on separate epithelia. Statistical analysis performed using student’s paired t-test, where p ≤ 0.05 is considered significant. We found that acute (3 min) basolateral TDCA treatment of Calu-3 cells stimulated basal Isc by 35 ± 7% (p = 0.0029, n = 9) but had no effect on the Isc responses induced by carbachol or forskolin treatment. In contrast, acute apical treatment (30 min) of Calu-3 cells with DCA had no effect on basal Isc or on forskolin-stimulated Isc but did attenuate the Isc responses to carbachol by 43 ± 8% (p = 0.001, n = 7). In contrast, prolonged (24 hr) bilateral treatment with DCA or TDCA did not significantly alter either basal, forskolin- or carbachol-induced Isc. In order to determine if the increased Isc observed after TDCA treatment was as a result of local ATP release, experiments were repeated in the presence of hexokinase (24 U/ml) added either before or after TDCA. However, hexokinase did not significantly attenuate TDCA stimulated current indicating that ATP is unlikely to be a cellular medicator of bile acid action on airway ion transport. Western blotting showed that Calu-3 cells express the bile acid receptor, farnesoid X receptor (FXR). Chronic (24 hr) apical treatment of Calu-3 with an FXR agonist, GW4064 (5 μM), induced a 30 ± 11 % increase in FXR expression (p = 0.0306, n = 4). In summary, our data show that bile acid modulation of airway ion transport depends on the sidedness and duration of exposure, and the conjugated/unconjugated form of the bile acid. Further investigations are required to determine the role of the bile acid receptor FXR and the ion channels contributing to DCA and TDCA effects in modulating airway epithelium ion transport.