We examined the effects of a chronic increase in tubular sodium delivery on the structure of the distal convoluted tubule (DCT), connecting tubule (CNT), and cortical collecting duct of male Sprague-Dawley rats. Furosemide (12 mg/day) was administered by osmotic minipump for 6 days to increase the rate of sodium delivery to these segments and thereby stimulate sodium uptake. To prevent volume depletion, the furosemide-treated animals were given a drinking solution containing 0.8% NaCl and 0.1% KCl. Control animals were given vehicle (0.9% NaCl) by osmotic minipump and they drank tap water. Furosemide dramatically increased urinary fluid and sodium excretion and decreased urine osmolality threefold vs. control. Furosemide treatment was associated with an increase in epithelial volume of DCT cells, CNT cells, and principal cells and an increase in the basolateral membrane area and mitochondrial volume of each cell type. These alterations in cell structure were not related to changes in plasma aldosterone, glucocorticoid, or arginine vasopressin levels. We conclude that an increase in cell sodium uptake regulates the ultrastructure of the distal tubule.