We demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2. Using immunoblot and immunohistochemistry, we demonstrated that claudin 2 has a 4-fold greater abundance in neonatal proximal tubules than in adult tubules. Occludin, however, has a 4-fold greater expression in adult tubules than in neonatal tubules. Administration of thyroid hormone to neonates did not affect claudin 2 expression, occludin expression, or the transepithelial resistance in rat proximal tubule cells in vitro. In conclusion, there are postnatal maturational changes in tight junction proteins. The factors that cause these maturational changes are unknown but unlikely to be due solely to the maturational increase in thyroid hormone.The proximal tubule receives an ultrafiltrate from the glomerulus and reabsorbs two thirds of the ultrafiltrate in a nearly iso-osmotic manner. In addition to active transcellular fluid transport, the proximal tubule reabsorbs solutes via passive diffusion across the paracellular pathway. The early proximal tubule reabsorbs glucose and amino acids and preferentially reabsorbs bicarbonate over chloride ions (1,2), which leaves the luminal fluid delivered to the late proximal tubule with a higher chloride concentration and lower bicarbonate concentration than that in the peritubular plasma (1,2). Passive solute transport is dependent on the gradients that develop between lumen and peritubular capillary and permeability properties of the paracellular pathway.Approximately two thirds of the filtered chloride is reabsorbed by the adult proximal tubule (1,3 active and transcellular and half is passive and paracellular (3-5). Active NaCl transport is mediated by the parallel operation of the Na+/H+ exchanger and a Cl−/base exchanger (3,4). Passive Cl absorption is mediated by diffusion of chloride ions down its concentration gradient generated in the early proximal tubule (6,7). Thus, the permeability properties of the paracellular pathway can affect a significant amount of proximal tubule NaCl transport.Furthermore, the permeability properties of the paracellular pathway serve as a barrier to prevent the back diffusion of glucose, amino acids, phosphate, bicarbonate, and other solutes that are in higher concentration in the peritubular fluid than in the lumen of the late proximal tubule. In previous in vitro rabbit microperfusion studies, our laboratory demonstrated that unlike the adult segment, the neonatal proximal tubule was impermeab...