1. Potential differences across the mucosal or outer, and the serosal or inner, membranes of the toad skin (M and S) were recorded separately. Total potential difference across the skin (T) and the short-circuit current (SCC) were recorded by means of the classical Ussing method. 2. The independent determination of the M and the S is of importance in the elucidation of the mechanism of action of agents which alter ion fluxes across the skin. 3. The percentage values of the M and the S obtained in toad skins during the summer were similar to the percentage values obtained by microelectrode impalement of cells. 4. Angiotensin II (AII) and antidiuretic hormone (ADH) increased T with a notable rise in M and a slight increase in S. These agents act mainly by increasing mucosal membrane permeability to Na+ since M is principally affected. 5. Amiloride and ouabain reversed M, decreased T and increased S above T. The reversal of M might be explained by the flow of a cation to the mucosal aspect or of an anion to the cell interior. 6. These results show that the effects of several agents on the toad skin potential may be analysed independently across the mucosal and serosal membranes and reflect the behaviour of the entire tissue rather than of a single cell.