To investigate the possible role of a Na transport defect in the pathogenesis of the phosphaturia in vitamin D resistant rickets, we studied the activity of the Na-K ATPase activity along the microdissected segments of the nephron in normal (N) and hypophosphatemic mice (Hyp), the Na uptake by renal brush border membrane (BBM), as well as the interrelationship between Na and phosphate transport through this membrane. In N mice, Na-K ATPase activity was present in decreasing order, in the distal tubule, the ascending branch of the loop of Henle, the proximal tubule, and the collecting tubule. In Hyp mice, the Na-K ATPase activity was comparable to that measured in N mice, except in the granular segment of the distal tubule where a 256% of the control activity was reproducibly observed. In N mice, Na initial uptake by BBM vesicles increased with Na concentration in the incubation medium, according to two kinetic components: one saturable, evident at low substrate concentrations and the other, nonsaturable, corresponding to a passive diffusion. The addition of 5 mM PO4 in the incubation medium did not significantly influence Na transport. In contrast, Na concentration in the incubation medium largely modified the kinetics of PO4 uptake: increasing Na concentration enhanced PO4 uptake and decreased the apparent Km. In Hyp mice, Na uptake by BBM was identical to that observed in N mice, but PO4 uptake was decreased by half. Na concentration in the incubation medium similarly influenced PO4 uptake in N and Hyp mice, and the Km values at each concentration of Na were comparable in the two series of animals.(ABSTRACT TRUNCATED AT 250 WORDS)