Effects of neuropeptides of the vasopressin family on Cl - secretion have not yet been reported in lung. Using the 16HBE14o- bronchial epithelial cell line, we investigated their action on Cl - secretion. In symmetrical Cl - solutions, basolateral application of arginine vasotocin (AVT), oxytocin or isotocin induced a transient I sc stimulation (I peak), whereas arginine vasopressin (AVP) did not. The effects of different Cl - channel blockers and of a protein kinase C (PKC) inhibitor suggest that CFTR is involved in I peak. The calcium-activated K + channel (SK4) and the Cl -/HCO 3- exchanger favor the driving force for AVT-mediated Cl - secretion. The antagonists of V1a (SR49059)- and V1b (SSR149415)-receptors blocked I peak, while SR121463B, a V2 receptor antagonist, did not. These results point to the stimulation of a V1-like receptor mediating I peak and presenting an efficacy order, AVT > oxytocin > isotocin ≫ AVP. When a serosal to mucosal Cl - gradient was applied, AVT and AVP both stimulated I sc according to a biphasic profile, I peak being followed by a plateau phase (I plateau). The pharmacology of I plateau suggests that CFTR channels are involved and that Na +/K +/2Cl - is the only transporter associated with I plateau. dDAVP, a V2 receptor agonist-induced I plateau with the same potency as AVP, suggesting the involvement of V2 receptors in the AVP-induced I plateau. V2 receptors are present on both opposite membranes, while V1-like receptors are mainly expressed on the basolateral membranes. RT-PCR experiments show the expression of V1a, V1b, V2 and vasopressin-activated calcium-mobilizing (VACM) receptors mRNAs. © 2005 Nature Publishing Group All rights reserved.