Net proton secretion and unidirectional chloride fluxes were measured in isolated skin of toads (Bufo bufo) and frogs (Rana esculenta) mounted in an Ussing chamber and exposed to a Ringer's solution on the serosal side and a freshwater-like solution (1-3 mM Cl^-) on the external side. Active proton secretion was 34.2-2.0 pmol·cm^-2·s^-1 (n=18) in frog skin, and 16.7-1.7 pmol·cm^-2·s^-1 (n=10) in toad skin. Proton secretion by toad skin was dependent on the transepithelial potential (V_T), and an amiloride-insensitive short-circuit current was stimulated by exogenous CO₂/HCO₃^-, indicating the presence of a rheogenic proton pump. Cl^- influx was 37.4-7.5 pmol·cm^-2·s^-1 (n=14) in frog skin and 19.5-3.5 pmol·cm^-2·s^-1 (n=11) in toad skin. In toad skin, the mean Cl^- flux ratio was larger than expected for simple electro-diffusion. In 8 of 11 sets of paired skins, influx was greater than the efflux indicating active uptake of Cl^-. Cl^- influx in toad skin was unaffected by large perturbations (100-150 mV) of V_T, which was accomplished by adding amiloride to the outer bath under open circuit conditions. A component of the Cl^- efflux seemed to be dependent on V_T. 4,4'-Diisothiocyanato-stilbene-2,2'-disulfonic acid (DIDS; 0.3 mM or 1.3 mM) inhibited Cl^- influx and, surprisingly, increased Cl^- efflux in toad skin. Influx and efflux of Cl^- in toad skin were highly dependent on the external [Cl^-] in the freshwater range (0.1-4 mM). ³⁶Cl^- influx decreased whereas the total Cl^- efflux increased as a function of external [Cl^-]. These data indicate the presence of a DIDS-sensitive, electroneutral carrier mechanism with an external binding site for Cl^-. Ethoxzolamide (100 µM), an inhibitor of carbonic anhydrase, reduced proton secretion and Cl^- influx in frog skin. Concanamycin A (0.1-10 µM), a specific vacuolar-type proton pump (V-ATPase) inhibitor, significantly reduced proton secretion in frog skin. In addition, concanamycin A (1 µM) significantly reduced Cl^- influx in frog skin. We suggest that the active proton secretion and Cl^- influx are coupled. We hypothesise that an apical V-ATPase is capable of energising active Cl^- uptake in fresh water by creating a favourable gradient for an apical HCO₃^- exit in exchange for external Cl^-. The data also suggest that a carbonic anhydrase activity provides H⁺ and HCO₃^- for apically co-expressed proton pumps and Cl^-/HCO₃^- exchangers.