The properties of two sodium-dependent D-glucose transporters previously identified in renal proximal tubule brush border membrane (BBM) vesicles are studied. The low-affinity system, found in BBM vesicles from the outer cortex (early proximal tubule), is shown to be associated with the high-affinity phlorizin binding site typically found in renal BBM preparations. The high-affinity system, found in BBM vesicles from the outer medulla (late proximal tubule), is almost two orders of magnitude less sensitive to inhibition by phlorizin and is apparently not associated with high-affinity phlorizin binding. The sodium/glucose stoichiometry of the outer medullary transporter is found to be 2:1 by two independent methods. Previous measurements have established that the stoichiometry of the outer cortical system is 1:1. It is suggested that this arrangement of transporters in series along the proximal tubule enables the kidney to reabsorb glucose from the urine in an energy-efficient fashion. The bulk of the glucose load is reabsorbed early in the proximal tubule at an energetic cost of one Na+ per glucose molecule. Then in the late proximal tubule a larger coupling ratio and hence a larger driving force is employed to reabsorb the last traces of glucose from the urine.