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1. The effects of antidiuretic hormone (ADH), theophylline and cyclic 3',5'-adenosine monophosphate (AMP) on membrane potentials in frog skin have been investigated.

2. Membrane potentials across the outer and inner facing membranes were recorded in both normal and current clamped skins. In the latter condition active transport of sodium had been abolished by ouabain or metabolic inhibitors, but ionic gradients were maintained by passing current through the skin from the inside.

3. ADH increases the potential across the outer facing membranes and reduces the skin resistance. The results are consistent with ADH causing an increase in permeability of the outer facing membranes to sodium ions.

4. Theophylline reduces the skin potential by reducing specifically the potential across the outer facing membranes. At the same time the skin resistance is reduced. Theophylline acts by increasing the permeability of the outer facing membranes to chloride ions.

5. Cyclic 3',5'-AMP causes a biphasic potential change accompanied by an increase in skin resistance.

6. Metabolic inhibitors block the response of the skin to ADH but not to theophylline.

7. Separate explanations for the increase in sodium transport by ADH, theophylline and cyclic 3',5'-AMP are discussed. It is not necessary to involve cyclic AMP in order to explain the effects of either ADH or theophylline.