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.

Substitution of chloride by isethionate reduces the short circuit current (SCC) and increases the potential of isolated frog skin. In sodium isethionate Ringer antidiuretic hormone and choline chloride increase the SCC, whereas theophylline is ineffective. Frog skins treated on the outside with copper ions always show an increased potential when bathed in normal Ringer solution. The SCC may be moderately increased or decreased. Theophylline increases skin thickness and cell volume in non‐short‐circuited skins. The ways in which the theophylline‐induced increase in chloride permeability affects sodium transport is discussed, together with the requirements for a permeant anion in both short‐ and open‐circuited skins.

The instantaneous impedance method has been used to study the effects of antidiuretic hormone (ADH) on frog skin. The resting skin may be represented by a parallel RC network with a single time constant. Antidiuretic hormone causes an increase in conductance and capacitance and in some cases the appearance of a polarization angle. The structures in the skin responsible for the transients are located in the outermost membranes. The effects of ADH have been interpreted in terms of the formation of water‐filled sodium‐permselective pores in the outer facing membranes which occupy, at most, 0.3% of the skin surface. These pores constitute a parallel, and hence additive, capacitance with that of the normally ion impermeable parts of the cell surface, and in addition are responsible for the increase in conductance. The polarization angle is due to the polydisperse nature of the skin after hormone treatment.

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The uptake of (±)‐[3H]noradrenaline from an aqueous phase to an ether phase containing dissolved lecithin has been measured. No differences between the behaviour of (+)‐ or (—)‐noradrenaline in this system could be detected. The biological implications of this finding are discussed.