The kidneys' major functions in regulating the acid-base balance of body fluids are to conserve plasma bicarbonate and replenish plasma bicarbonate lost in titration with nonvolatile acids. The proximal nephron reabsorbs the bulk of filtered bicarbonate, and, thus, predominates in the first function. The distal nephron forms the bulk of the net acid excreted, and, thus, predominates in the second function. A single mechanism, hydrogen ion secretion, is responsible for both functions. The renal tubular cells produce hydrogen and bicarbonate ions from the dissociation of intracellular carbonic acid catalyzed by intracellular carbonic anhydrase. The hydrogen ions are secreted into the lumen and simultaneously the bicarbonate ions move into the peritubular plasma. It is the details of the mechanism of hydrogen ion secretion and the control of hydrogen ion secretion which differ between the proximal and distal nephron segments. The purpose of this review is to describe these differences as elucidated by the technique of isolated perfused nephron segments.