The calcimimetic cinacalcet increases the sensitivity of the parathyroid calcium-sensing receptor to calcium and therefore should produce a decrease in the set point of the parathyroid hormone (PTH)-calcium curve. For investigation of this hypothesis, nine long-term hemodialysis patients with secondary hyperparathyroidism were given cinacalcet for 2 mo, the dosage was titrated per a protocol based on intact PTH and plasma calcium concentrations. Dialysis against low- and high-calcium (0.75 and 1.75 mM) dialysate was used to generate curves describing the relationship between PTH and calcium. Compared with precinacalcet levels, cinacalcet significantly reduced mean serum calcium, intact PTH and whole PTH (wPTH; all P < 0.001). The set points for PTH-calcium curves were significantly reduced, and both maximum and minimum levels of PTH (intact and whole) were significantly decreased. The calcium-mediated inhibition of PTH secretion was more marked after cinacalcet treatment. In addition, cinacalcet shifted the inverse sigmoidal curve of wPTH/non-wPTH ratio versus calcium to the left (i.e., less calcium was required to reduce the wPTH/non-wPTH ratio). In conclusion, cinacalcet increases the sensitivity of the parathyroids to calcium, causing a marked reduction in the set point of the PTH-calcium curve, in hemodialysis patients with secondary hyperparathyroidism.