This review summarizes recent progress in our understanding of the mechanisms of intracellular pH regulation, with particular emphasis on Na+-H+ countertransport. Methods developed for the measurement of cytoplasmic pH in small cells and their application to mammalian lymphocytes and neutrophils are described. The basic properties of the Na+-H+ antiport in these cells and its regulation by growth factors and tumor promoters will be discussed briefly. Finally, the significance of cytoplasmic pH regulation to cell function and survival will be considered.