The present in vitro microperfusion study compared the mechanism and rates of NaCl transport in neonatal and adult rabbit proximal straight tubules. In proximal straight tubules perfused with a late proximal tubular fluid and bathed in a serum-like albumin solution, the rate of volume absorption(Jv) was 0.54±0.10 and 0.12±0.05 nl/mm·min in adults and neonates, respectively (p<0.05). With the addition of 10-5M bath ouabain, Jv decreased to 0.27±0.07 and-0.03±0.04 nl/mm·min in adult and neonatal tubules, respectively(p<0.05), consistent with lower rates of active and passive NaCl transport in the neonatal proximal straight tubule. The rate of change of intracellular pH (pHi) in response to a change in luminal sodium and chloride concentration was used to assess the relative rates of Na+/H+ and Cl-/base exchange, respectively. The rates of Na+/H+ antiporter activity was 37.7±4.9 and 206.1±25.2 pmol/mm·min (p<0.01) in neonatal and adult proximal straight tubules, respectively. Cl-/base exchange was 6.0±1.2 and 45.7±6.6 pmol/mm·min (p<0.01) in neonatal and adult proximal straight tubules, respectively. In both neonatal and adult proximal straight tubules the rate of Cl-/base exchange was not affected by formate, bicarbonate, or cyanide and acetazolamide, but was inhibited by DIDS, consistent with Cl-/OH- exchange. These data demonstrate an increase in both active and passive proximal straight tubule NaCl transport during postnatal renal development. The increase in active NaCl transport is due to increases in both Na+/H+ antiporter and Cl-/OH- exchange activity.