During maturation of oocytes, Cl conductance (G_Cl) oscillates and intracellular pH (pH_i) increases. Elevating pH_i permits the protein synthesis essential to maturation. To examine whether changes in G_Cl and pH_i are coupled, the Cl channel ClC-0 was heterologously expressed. Overexpressing ClC-0 elevates pH_i, decreases intracellular Cl concentration ([Cl]_i), and reduces volume. Acute acidification with butyrate does not activate acid extrusion in ClC-0-expressing or control oocytes. The ClC-0-induced pH_i change increases after overnight incubation at extracellular pH 8.5 but is unaltered after incubation at extracellular pH 6.5. Membrane depolarization did not change pH_i. In contrast, hyperpolarization elevates pH_i. Thus neither membrane depolarization nor acute activation of acid extrusion accounts for the ClC-0-dependent alkalinization. Overnight incubation in low extracellular Cl concentration increases pH_i and decreases [Cl]_i in control and ClC-0 expressing oocytes, with the effect greater in the latter. Incubation in hypotonic, low extracellular Cl solutions prevented pH_i elevation, although the decrease in [Cl]_i persisted. Taken together, our observations suggest that KCl loss leads to oocyte shrinkage, which transiently activates acid extrusion. In conclusion, expressing ClC-0 in oocytes increases pH_i and decreases [Cl]_i. These parameters are coupled via shrinkage activation of proton extrusion. Normal, cyclical changes of oocyte G_Cl may exert an effect on pH_i via shrinkage, thus inducing meiotic maturation.