Xenopus laevis oocytes serve as a useful model system for investigating the mechanism of signal transduction of intrinsic responses in native oocytes and of acquired responses in oocytes injected with appropriate mRNAs from other tissues. This chapter describes the regulation of intracellular calcium activity in Xenopus oocytes. Native oocytes express several cell membrane receptors, stimulation of which, leads to the mobilization of calcium both from cellular stores and from the medium. Following the injection of mRNAs, a number of foreign receptors are expressed in oocytes that also use calcium mobilization to produce the physiologic response, such as activation of chloride channels. The effect of intracellular injections depends largely on the site and the depth of injection. Oocytes maintained in calcium-free medium often deteriorate rapidly owing to the activation of unspecified channels. Much greater activities of voltage-dependent calcium channels are expressed in oocytes injected with mRNA from various excitable tissues.