Receptor activator of NFB ligand (RANKL) is essential for osteoclast differentiation, and hormones and cytokines that stimulate bone resorption increase RANKL expression in stromal/osteoblastic cells. We have previously shown that parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) control murine RANKL gene expression in vitro, in part, via an evolutionarily-conserved transcriptional enhancer, designated the distal control region (DCR), located 76 kb upstream from the transcription start-site. Herein we describe the phenotype of mice lacking this enhancer. Deletion of the DCR reduced PTH- and 1,25(OH)₂D₃-stimulation of RANKL mRNA and osteoclast formation in primary bone marrow cultures, as well as stimulation of RANKL mRNA in bone. DCR deletion also reduced basal RANKL mRNA levels in bone, thymus, and spleen. Moreover, mice lacking the DCR exhibited increased bone mass and strength. The increase in bone mass was due to reduced osteoclast and osteoblast formation leading to a low rate of bone remodeling similar to that observed in humans and mice with hypoparathyroidism. These findings demonstrate that hormonal control of RANKL expression via the DCR is a critical determinant of the rate of bone remodeling.