The addition of the Ca2+ ionophore A23187 (1 microM) to the inside solution of the frog skin resulted in an approx. 40% transient increase in the active influx of Na+ and ionic conductance, which decayed to an approx. 13% steady-state stimulation after 1--2 h. A23187 had no effect from the outside solution. A23187's stimulatory action is most likely the result of the ionophore's ability to increase intracellular Ca2+. This contention is supported by the following experimental results: (1) reintroduction of Ca2+ into a Ca2+-free inner solution stimulated Na+ transport only in the presence of A23187: (2) Mg2+ would not mimic these effects, and (3) EGTA in the inner solution would inhibit the A23187 response. The stimulation of active transport and ionic conductances elicited by A23187 were found to be very similar to those caused by antidiuretic hormone. Several lines of evidence suggest that A23187 may by-pass steps in the normal antidiuretic hormone stimulatory process: (1) A23187 and antidiuretic hormone are apparently non-additive; (2) A23187 acts three times faster than antidiuretic hormone; (3) A23187 stimulates antidiuretic hormone-insensitive frog skins, and (4) results from other laboratories indicate that A23187 does not increase cyclic AMP concentrations. It is speculated that an increase in free intracellular Ca2+ may be a step in the normal antidiuretic hormone stimulatory process. This increase in intracellular Ca2+ may in turn stimulate active sodium transport by increasing the Na+ permeability of the outer 'rate-limiting' membrane.