Ion transport by the airway epithelium contributes to the regulation of the quantity and composition of respiratory tract fluid, thereby affecting mucociliary clearance. We have investigated the effect of the mucoactive drug S-carboxymethylcysteine-lysine salt (S-CMC-Lys) on the transepithelial bioelectric properties of isolated rabbit trachea. Transepithelial potential difference (Vms), short-circuit current (Isc) and resistance (R) were measured in the isolated rabbit trachea mounted between flux half-chambers, in the presence and in the absence of S-CMC-Lys (100 microM), added to the mucosal or submucosal chamber. In some experiments, tissues were also exposed to ion channel-inhibitors, in order to evaluate the contribution of Na+ and Cl- active transport to Isc. The excised rabbit trachea expressed transepithelial bioelectric properties based on an active ion transport supported by the Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, since ouabain (500 microM) completely abolished the transepithelial potential difference. In control preparations, Vms and Isc declined significantly during 300 min recording, whereas R remained constant. The Isc decline was essentially attributable to a decrease in Cl- transport. Bumetanide (100 microM) almost completely abolished the Isc fraction related to Cl- transport. Treatment of the tissues with S-CMC-Lys reduced the progressive fall in Isc, with the most clear-cut and significant effect observed for the mucosal treatment. In parallel, S-CMC-Lys significantly lowered R, without affecting Vms. Either mucosal or submucosal exposure to S-CMC-Lys significantly increased Cl- secretion to normal values, whilst Na+ absorption was not modified.(ABSTRACT TRUNCATED AT 250 WORDS)