The apical secretion of chloride by the CFTR (cystic fibrosis transmembrane conductance regulator) is the driving force for sodium and water flux across epithelia. Most of the water flows through the paracellular shunt. However, it is yet unclear if and to which extent the paracellular permeability is regulated by CFTR. Upon stimulation with cAMP CFTR is inserted in the apical membrane where it forms multiprotein-clusters with a huge variety of proteins and enzymes. Some of these enzymes interact with tight junction proteins and / or with the cytoskeleton. We propose that these CFTR multiprotein-clusters regulate the paracellular permeability of epithelia. We measured the transepithelial electrical resistance (TEER) of human bronchial epithelial cell lines expressing wtCFTR (16HBE14o-) and F508del-CFTR (CFBE41o-). Stimulation with cAMP reduces the TEER of 16HBE14o- cells by 52.7 ± 2.5 % (n=6) whereas the TEER of F508del-CFTR expressing cells (CFBE41o-) shows an increase of 19 ± 3.6 % (n=7) upon stimulation. The CFTR specific inhibitor, CFTRInh-172 exerts little effects on the cAMP induced TEER changes. Taken together, the results indicate that CFTR regulates the paracellular permeability.