Oocytes grow within ovarian follicles, and only gain the ability to complete meiosis when they are nearly fully grown. We have found that both of the major types of intracellular pH regulatory mechanisms in the mammal-the Na+/H+ and HCO3-/Cl- exchangers-were essentially inactive in mouse oocytes over most of the course of their growth. However, as oocytes approached full size, Na+/H+ and HCO3-/Cl- exchangers became simultaneously active, and, at the same time, the intracellular pH of isolated oocytes increased sharply by about 0.25 pH unit. This activation of intracellular pH regulatory mechanisms and increase in pH occurred coincident with the acquisition of meiotic competence. The activation of pH regulatory mechanisms during oocyte growth represents a previously unknown milestone in the development of the capacity of the oocyte to function independently upon ovulation. (c) 2005 Elsevier Inc. All rights reserved.