Administration of glucocorticoids to neonates increases proximal tubule volume absorption by increasing glucose, bicarbonate, and amino acid transport. We have recently demonstrated that glucocorticoids may contribute to the maturational decrease in phosphate transport. This study examines the maturation of NaPi-6 [the regulated proximal tubule sodium-inorganic phosphate (Na-Pi) transporter] mRNA and protein abundance and the mechanism for the decrease in phosphate transport by glucocorticoids. Weaned young rabbits (5 wk) had a 2-fold greater brush border membrane NaPi-6 protein abundance than that measured in adults. Renal cortical NaPi-6 mRNA abundance was comparable in neonates (less than 10 d of age) and adults. Renal brush border membrane vesicles from dexamethasone-treated neonatal rabbits (10 micrograms/100 g of body weight for 4 d) had a lower rate of Na-Pi transport than vehicle-treated controls (46.8 +/- 6.5 versus 71.0 +/- 9.0 pmol 32P/10 s/mg of protein, p < 0.05). Abundance of NaPi-6 protein in brush border membrane vesicles was 3-fold lower in newborn rabbits treated with pharmacologic doses of dexamethasone than in vehicle-treated controls. NaPi-6 mRNA abundance was the same in both groups. NaPi-1, a brush border membrane phosphate transporter which is also an anion channel, mRNA, and protein abundance was not affected by glucocorticoids. These data demonstrate that there is a maturational decrease in NaPi-6 protein abundance and that glucocorticoids decrease neonatal phosphate transport, at least in part, by reducing the number of Na-Pi transporters.