The amphibian skin, widely used for studying the transepithelial passage of electrolytes, exhibits anion pathways relatively specific for Cl − . We studied the effect of HgCl 2 , 1.0×10 −4 M on its electrical parameters and unidirectional anion fluxes. In the presence of Cl − , the transepithelial conductance (G) of the isolated skin of the Bufo arenarum toad increased considerably following exposure to HgCl 2 , whereas short-circuit current (SCC)—reflecting transepithelial Na + transport—underwent only slight stimulation. Following the blockade of Na + intake by amiloride, 1.0×10 −4 M, the removal of Cl − from the solution bathing the epidermal border of the skin brought about a decrease in G, and gave rise to a gradient-induced SCC (SCCg) consistent with transepithelial passage of Cl − along its gradient. Addition of mercaptoethanol, 5.0×10 −3 M to the bath containing Hg 2+ fully reversed these effects. The increase in G was accompanied by an increase in the unidirectional (epidermal to dermal) fluxes of 36 Cl − and 131 I − , and a decrease in the passage of 99m TcO 4 − . These results show the effects of HgCl 2 to be similar to those of theophylline, although exhibiting a different selectivity. Our data suggest that anion passage following exposure to HgCl 2 is, like that stimulated by theophylline, predominantly if not exclusively transcellular, and does not involve a significant opening of the tight junctions.