Chloride transport across amphibian skin epithelium includes a time dependent voltage-activated conductance (GCl) localized to a small moiety of mitochondria-rich cells. The pathway, activated by serosal positive potential, is stimulated by increased cellular cAMP. Different responses were obtained in skins of Bufo viridis Bufo bufo and Rana pipiens, Therefore, we compared these species to clarify the observations. Skins from all species respond on ß-adrenergic stimulation, on application of the cAMP analogue, CPT-cAMP and xanthines (IBMX), alas in different ways. While activated GCl in R. pipiens skin retained its properties in response to increased cellular cAMP at all conditions, GCl in B. viridis skin increased and changed its qualitative properties on application of CPT-cAMP at supramximal concentrations. Specifically, the sensitivity to voltage was almost lost and change of its anion selectivity allowed the passage of NO3 in the pathway. B. bufo skin responded similarly, but to a lesser extent. Epinephrine inhibits the activated GCl in all species, but to a smaller degree in the skin of R. pipiens compared with the 2 toads species. The activated GCl system is believed to be composed of 2 components, a translocating anion selective channel, governed by a voltage-sensitive regulator. The two mentioned components and the distinctive regulation can explain the observed differences in the response of GCl among the skins of the species investigated.