Because the pathogenesis of osteosclerosis in hypervitaminosis D is still not well elucidated, the authors experimentally studied hypervitaminosis D3 in 66 rabbits by injecting different doses of vitamin D3. Contact radiographs of bone specimens showed various signs of osteosclerosis, including dense epiphyses and metaphyses, thickened bony articular surfaces, dense metaphyseal bands, modeling defects at the metaphysis, and dense and thickened cortical bone. The corresponding pathologic sections showed that conspicuous metastatic calcification coated the trabeculae and filled bone marrow cavity and caverns in the original but porotic cortical and periosteal new bone. Rather than being resorbed, the metastatic calcifications were embedded in a thick layer of newly formed bone 6 to 14 weeks after vitamin D3 withdrawal. This study suggests that in hypervitaminosis D3, the osteoblasts and bone marrow undergo degeneration, leading to necrosis and calcification. After vitamin D3 withdrawal, osteoblasts reappear and become overactive, leading to overossification.