Inositol phosphate action in an intact cell has been investigated by intracellular microinjection of eight inositol phosphate derivatives into Xenopus laevis oocytes. These cells have calcium-regulated chloride channels but do not have a calcium-induced calcium release system. Microinjection of inositol 1,3,4,5-tetrakisphosphate (IP4), inositol 1,2-(cyclic)-4,5-trisphosphate (cIP,), inositol 1,4,5trisphosphate (IP,), or inositol 4,5-bisphosphate [(4,5)IP,], open chloride channels to induce a membrane depolarization. However, inositol 1-phosphate (IP,), inositol 1,3,4,5,6-pentakisphosphate (IP5), inositol 1 ,4-bisphosphate, or inositol 3,4-bisphosphate are unable to induce this depolarization. The depolarization is mimicked by calcium microinjection, inhibited by EGTA coinjection, and is insensitive to removal of extracellular calcium. By means of the depolarization response, the efficacy of various inositol phosphate derivatives are compared. IP, and cIP3 induce similar half-maximal, biphasic depolarization responses at an intracellular concentration of approximately 90 nM, whereas IP, induces a mono-or biphasic depolarization at approximately 3400 nM. At concentrations similar to that required for IPS and cIP,, (4,5)IP2 induces a long-term (greater than 40 min) depolarization. The efficacy (CIP, = IP, = (4,5)IP, >> IP,) and action of the various inositol phosphates in an intact cell and their inability to induce meiotic cell division are discussed.