Proton secretion in frog skin is mediated by an electrogenic H + pump. Pharmacological and immunocytological approaches have identified this pump as belonging to the V-ATPase class. The key role of this V-ATPase in proton secretion (acid-base balance) and as a membrane energizer of other solute transport from very dilute solutions is outlined. It is shown that the frog skin constitutes a model of a V-ATPase-dependent Na + transport mechanism applicable to other freshwater animals. On the other hand, attempts to implicate the V-ATPase in the active urea transport that develops through the skin of salt-adapted frogs have failed; the nature of the different urea transporters located on apical and basal epithelial cell membranes and those responsible for active urea reabsorption remain to be identified.