The calcium-sensing receptor (CaR) helps to maintain the homeostasis of extracellular calcium by controlling the secretion of hormones associated with this process. The mechanism of agonist-induced endocytosis and downregulation of CaR and the influence of this event on the secretion of CaR-regulated hormones is not fully understood. In this study, we show that CaR is constitutively endocytosed and recycled to the plasma membrane by a Rab11a-dependent mechanism; during this process, the level of total cellular CaR is maintained. This trafficking of CaR promotes the secretion of parathyroid hormone-related peptide (PTHrP), as evidenced by a decrease on PTHrP secretion in the presence of a dominant negative mutant of Rab11a. Interestingly, this Rab11a dominant negative mutant does not interfere with CaR-dependent activation of extracellular signal-related kinase (ERK) 1/2, suggesting that ERK signaling is not sufficient to promote PTHrP secretion downstream of CaR. In addition, AMSH, a CaR carboxyl-terminal binding protein, redirects CaR from slow recycling to downregulation, reducing CaR expression and decreasing PTHrP secretion. Our results indicate that endocytosis and trafficking of CaR modulate PTHrP secretion.