Lung epithelia are covered by a liquid layer, which is crucial for gas exchange and host defense. Its viscosity depends on ion transport mechanisms involving apical Na+ and Cl- channels. In our present study we used freshly isolated lung preparations of Xenopus laevis as a model for alveolar epithelia to investigate transepithelial Cl- transport mechanisms. Flux measurements revealed, that, besides Cl- secretion mechanisms, also Cl- reabsorption mechanisms exist in this epithelia. In Ussing chamber experiments the basolateral application of the loop diuretics furosemide and bumetanide was without significant effects, indicating that under basal conditions the Na+ /K+ /2Cl-- cotransporter (NKCC) is not a meaningful pathway for basolateral Cl- uptake. However, under apical Cl- free conditions in order to increase the driving force for luminal Cl- secretion, the diuretics significantly decreased Isc , indicating the presence and involvement of a basolateral NKCC. The apical application of the thiazide diureticum chlorthalidone, a common blocker of Na+ /Cl- cotransporters (NCC), led to a significant decrease of Isc under basal conditions, thereby indicating that a NCC is involved in luminal Cl- reabsorption. Interestingly, the effect was prevented by apical Cl- free conditions. Taken together, these data indicate that Cl- secretion via luminal Cl- channels depends on Cl- uptake via different transport routes involving basolateral located NKCCs as well as apical NCCs. Supported by DFG FR2124