1,25-Dihydroxyvitamin D₃ [1,25(OH)₂D₃] is a principal regulator of calcium and phosphorus homeostasis through actions on intestine, kidney, and bone. 1,25(OH)₂D₃ is not considered to play a significant role in bone formation, except for its role in supporting mineralization. We report here on the properties of 2-methylene-19-nor-(20S)-1α,25(OH)₂D₃ (2MD), a highly potent analog of 1,25(OH)₂D₃ that induces bone formation both in vitro and in vivo. Selectivity for bone was first demonstrated through the observation that 2MD is at least 30-fold more effective than 1,25(OH)₂D₃ in stimulating osteoblast-mediated bone calcium mobilization while being only slightly more potent in supporting intestinal calcium transport. 2MD is also highly potent in promoting osteoblast-mediated osteoclast formation in vitro, a process essential to both bone resorption and formation. Most significantly, 2MD at concentrations as low as 10⁻¹² M causes primary cultures of osteoblasts to produce bone in vitro. This effect is not found with 1,25(OH)₂D₃ even at 10⁻⁸ M, suggesting that 2MD might be osteogenic in vivo. Indeed, 2MD (7 pmol/day) causes a substantial increase (9%) in total body bone mass in ovariectomized rats over a 23-week period. 1,25(OH)₂D₃ (500 pmol three times a week) only prevented the bone loss associated with ovariectomy and did not increase bone mass. These results indicate that 2MD is a potent bone-selective analog of 1,25(OH)₂D₃ potentially effective in treating bone loss diseases.