The role of Ca2+ on the depolarization-induced appearance of a Na+ current in Xenopus oocytes was studied. Oocytes were voltage-clamped and the induction of the Na+ current was tested under various conditions. In oocytes pre-injected with 400 pmol EGTA to increase the intracellular Ca2+ buffering power, the current was significantly reduced. Conversely, when intracellular Ca2+ was made to increase by injecting an analogue of inositol 1,4,5-trisphosphate (3-F InsP3), to cause Ca2+ release from internal stores, the induction of the Na+ current was potentiated. The depolarization-inducible Na+ channels of the Xenopus oocyte membrane appear, therefore, to be Ca2+ sensitive, as well as depolarization-activated.