The effect of Ba 2 + on basolateral membrane conductance (gl) in isolated frog skins was analysed. Response patterns were different in tissues with high and low spontaneous intraceltular potential. At high (negative) potentials, serosat Ba 2 + inhibited gi as is expected of a potent K + channel blocker, whereas in tissues with tow potential, g~ remained unchanged or even increased after Ba 2 +. The direction of change in gi was also dependent on the magnitude ofgi under control conditions. Decrease of gl was only observed at high gi in the control period. In contrast, g~ increased if control values of gi were below 0.5 mS/cm 2. In tissues with spontaneously low intracellular potential, an inhibitory effect of Ba 2 + on g~ could be induced by hyperpotarization of the basolateral membrane with transepithetial voltage perturbation. Under these conditions, voltage-dependent, inward rectifying K + channels are activated, which are Ba2+-sensitive. Furthermore, hyperpolarization of the basolateral membrane potential (P]) during Ba z+ rapidly decreased gi-These results suggest that Ba z +, in addition to blocking K + channels, activates (presumably unspecific) basolateral membrane channels. This dual effect, which is obvious in tissues with low spontaneous g~, might similarly exist in tissues with high control gi. Identification, however, is virtually impossible due to the large decrease in potassium conductance.