Dietary Pi and parathyroid hormone (PTH) are two most important physiological and pathophysiological regulators of Pi re-absorption in the renal proximal tubule. Effects of dietary Pi on Na+/Pi co-transporter NaPi-2 were investigated in thyroparathyroidectomized (TPTX) rats. NaPi-2 protein and mRNA in the kidney cortex of TPTX rats were increased approximately 3.8- and 2.4-fold in amount respectively compared with those in the sham-operated animals. Administration of PTH to the TPTX rats resulted in a decrease in the amount of NaPi-2 protein, but not in the abundance of NaPi-2 mRNA. Deprivation of dietary Pi in the TPTX rats did not affect the amount of NaPi-2 mRNA and protein. In the Pi-deprived TPTX rats, feeding of a high-Pi diet resulted in marked decreases in Pi transport activity and the amount of NaPi-2 protein in the superficial nephrons. Immunohistochemical analysis demonstrated that administration of PTH to TPTX rats resulted in a decrease in NaPi-2 immunoreactivity from both superficial and juxtamedullary nephrons within 4 h. Switching TPTX animals from a low-Pi diet to the high-Pi diet decreased NaPi-2 immunoreactivity from superficial nephrons, but not from juxtamedullary nephrons, within 4 h. These results suggest that dietary Pi could regulate the amount of NaPi-2 protein in the superficial nephrons in a PTH-independent manner.