During the meiotic maturation of oocytes, chloride conductance (G_Cl) oscillates and intracellular pH (pH_i) increases. Elevating pH_i is thought to permit the protein synthesis essential to maturation. To examine whether changes in G_Cl and pH_i are coupled, the chloride channel, ClC-0, was heterologously expressed. Over-expression of ClC-0 elevates pH_i and decreases intracellular Cl concentration ([Cl]_i). Additionally, expression of ClC-0 reduced cell volume as indicated by a 30% reduction in oocyte water content. Acute acidification with 5 mM butyrate does not activate acid extrusion mechanisms in either ClC-0 expressing or control oocytes. The magnitude of the ClC-0 induced pHi change increases after overnight incubation at pH_o 8.5, but does not change after incubation at pH_o 6.5. Membrane depolarization ([K⁺]_o = 25 mM) did not change pH_i. In contrast, hyperpolarization ([K⁺]_o= 0.1 mM) elevates pH_i. Thus, neither membrane depolarization nor acute activation of acid extrusion can account for the ClC-0 dependent alkalinization. ClC-0 expression decreases [Cl]_i compared to control oocytes. Overnight incubation in low [Cl]_o increases pH_i and decreases [Cl]_i in control and ClC-0 expressing oocytes, with the effect greater in the latter. Moreover, the V_m of ClC-0 expressing oocytes remains ~ -30 mV, indicating effective chloride depletion. Incubation in hypotonic, low [Cl]_o solutions prevented pH_i elevation, although the decrease in [Cl]_i persisted. Taken together with the observations that low [Cl]]_o and [K]]_o increase pH_i, this suggests that KCl loss leads to the observed oocyte shrinkage, which in turn transiently activates an acid extrusion pathway. In conclusion, expressing ClC-0 in Xenopus oocytes increases pH_i and decreases [Cl]_i. These parameters are coupled via shrinkage-activation of a proton extrusion pathway. Normal, cyclical changes of oocyte G_Cl may exert an effect on pH_i via shrinkage, thus inducing meiotic maturation.