Renal proximal tubular reabsorption of phosphate (Pi) plays a critical role in the maintenance of phosphate homeostasis. Uptake of Pi occurs at the apical cell surface of the proximal tubule via a sodium gradientdependent process (Na/Pi-cotransport). Transport across the basolateral membrane involves multiple pathways, including anion exchange mechanism and sodiumdependent Pi-cotransport, but is different from that in the apical membrane. The rate of proximal Pi reabsorption is adjusted acutely and chronically to the homeostatic needs of the body. In vivo and in vitro studies have provided evidence that physiological regulation of proximal tubular Pi reabsorption is most likely related to alterations in the transport capacity of apical membrane Na/Pi-cotransport (Murer et al., 1991; Dennis, 1992; Berndt & Knox, 1995; Biber & Murer, 1995). Recently type I Na/Pi-cotransporters from rabbit (Werner et al., 1991), mouse (Chong et al., 1994), and human (Miyamoto et al., 1995) kidney cortex, and type II Na/Pi-cotransporters from rat and human (Magagnin et al., 1993), rabbit (Verri et al., 1995) and mouse (Collins & Ghishan, 1994; Hartmann et al., 1995) kidney cortex, flounder kidney (Werner, Murer & Kinne, 1994), OK cells (Sorribas et al., 1994), and bovine renal NBL-1 cells (Helps, Murer & McGivan, 1995) have been identified by expression cloning, and polyclonal antibodies have been raised against the C-and N-terminals of the predicted peptide sequences. Subsequent studies have provided evidence that the type II rather than the type I Na/Pi-cotransporter represents a target for the physiological and pathophysiological regulation of proximal tubular reabsorption of Pi. This review article will, therefore, describe the basic characterization and transport characteristics of the type II Na/Pi-cotransporter and its regulation by parathyroid hormone and dietary Pi, the two most important physiological and pathophysiological regulators of renal proximal tubular Pi reabsorption.