Treatment of ventral frog skin with serosal A23187 calcium ionophore caused an initially transient increase in transepithelial sodium transport. After 60 min of treatment with A23187, a steady-state transport value was reached which was significantly lower than the initial one. Furthermore, it was found that ionophore treatment greatly inhibited the natriferic response to ADH and to 8br-cAMP. A further analysis on the possible ionophore action mechanism was carried out through pretreatment of the skin with indomethacin, very powerful prostaglandin synthesis inhibitor. In the experimental conditions reported, A23187 seems no longer capable of inducing a transient increase in sodium transport, although it does inhibit the natriferic response to ADH.