We have recently demonstrated that the rates of both active and passive proximal straight tubule (PST) NaCl transport in neonatal rabbits were less than in adults. In this segment NaCl entry across the apical membrane is via parallel Na + /H + and Cl − /OH − exchangers, which increases in activity with maturation. The present in vitro microperfusion study examined whether thyroid hormone plays a role in the maturational increase in PST NaCl transport. Neonatal and adult PST were perfused with a high-chloride-low bicarbonate solution without organic solutes, simulating late proximal tubule fluid. Thyroid hormone-treated neonates had a higher rate of PST total and passive NaCl transport. In 8-wk-old animals that were hypothyroid since birth, the maturational increase in total and passive NaCl transport was prevented. Thyroid treatment for 4 days in hypothyroid 8-wk-old rabbits increased the rate of both total and passive NaCl transport. The maturational increases in both Na + /H + and Cl − /OH − exchange activities were blunted in 8-wk-old hypothyroid animals and increased to control levels with thyroid treatment. This study demonstrates that thyroid hormone is a factor responsible for the maturational increase in both active and passive PST NaCl transport.Keywords sodium/hydrogen antiporter; chloride/base exchanger; kidney development; passive transportThe Proximal Tubule Reabsorbs ~60% of the filtered NaCl. The preferential reabsorption of organic solutes and bicarbonate by the early proximal tubule leaves the luminal fluid with a higher chloride and lower bicarbonate concentration than the peritubular plasma (19,24). In the proximal tubule approximately one-half of NaCl transport is passive and paracellular (4,25). The parallel operation of the apical membrane Na + /H + antiporter and Cl − /base exchangers mediate NaCl entry into the proximal tubule cell (1,18,25 We have recently examined the postnatal developmental changes in proximal straight tubule (PST) NaCl transport (25). In rabbit PST perfused with a high chloride-low bicarbonate solution simulating late proximal tubular fluid and bathed in a serum-like albumin solution, the rate of volume absorption, a reflection of both active and passive NaCl transport, was over twofold higher in the adult than neonatal segment (25). NaCl transport was inhibited by 50% by bath ouabain in adult tubules and totally inhibited in the neonatal segment. Thus the rates of active and passive NaCl transport were higher in the adult tubule than were those in the neonate (25).In the rabbit PST there was a fivefold increase in the Na + /H + antiporter activity during postnatal development (25). Cl − /base exchange in neonatal and adult PST was not affected by cyanide and acetazolamide, CO 2 and bicarbonate, or the addition of formate, consistent with Cl − /OH − exchange (18, 25). There was a sixfold maturational increase in apical membrane PST Cl − /OH − exchange activity (25).The factors that produce the profound postnatal changes in active and passive proximal tubular t...