Renal phosphate reabsorption is tightly regulated by several factors including parathyroid hormone (PTH). Acute application of PTH causes phosphaturia due to decreased proximal tubular phosphate reabsorption. Two isoforms of the type II sodium- dependent phosphate transporter SLC34 family are expressed in the brush border membrane of the proximal tubule, NaPi-IIa and NaPi-IIc. PTH induces the rapid retrieval of NaPi-IIa from the brush border membrane and subsequent lysosomal degradation. Mutations in NaPi-IIc have been recently demonstrated in patients with hereditary hypophosphatemic rickets with hypercalciuria due to excessive renal phosphate wasting. Here, we studied the effect of PTH on NaPi-IIc in wildtype and NaPi-IIa deficient mice. PTH induced a time-dependent retrieval of NaPi-IIa within 5-10 min whereas no effect on NaPi-IIc was visible by immunohistochemistry up to 4 hrs after PTH application. Phosphate transport activity in brush border membrane vesicles decreased in WT mice after 1 and recovered after 4 hrs whereas in NaPi-IIa KO mice transport activity was stable after 1 hr and decreased after 4 hrs. NaPi-IIc abundance increased after 4 hrs in WT mice which may contribute to the normal transport activity whereas NaPi-IIa abundance remained low. Thus, the two phosphate cotransporter in the proximal tubule brush border membrane are differentially regulated by PTH.