Calcium homeostasis is altered in hypertensive patients. Indeed several investigators have reported that sodium-sensitive hypertension is associated with hypercalciuria. On the other hand, an independent clinical association exists between the occurrence of urolithiasis and hypertension, but the molecular mechanism(s) involved in stone formation by high blood pressure have not been so far clarified. To understand this association, it is obvious that we should analyze the effect of hypertension on the transport proteins involved in the renal calcium handling. In the kidney, the tubular reabsorption of calcium may proceed through transcellular and paracellular routes. At variance with the proximal tubule, along the distal segment, calcium transport is entirely sodium independent and occurs via the transcellular pathway. In particular, transcellular calcium reabsorption proceeds through a well-controlled sequence of events consisting of luminal calcium entry via the epithelial calcium channel (TRPV5), cytosolic diffusion of calcium bound to calbindin-D28K, and basolateral extrusion of calcium through the Na/Ca exchanger (NCX1) and plasma membrane Ca-ATPase (PMCA). It is highly likely that these proteins may be altered in hypertensive disease thus justifying and explaining the reported hypercalciuria. Experiments in hypertensive strains of animals exhibiting hypercalciuria may help to solve this puzzle.