Bacterial endotoxic reactions can cause osteonecrosis in humans by disseminated intravascular coagulation. The authors first used a combination of the Shwartzman reaction and corticoid injections in rabbits to develop a new animal model of osteonecrosis. This model showed a significantly higher incidence and wider area of osteonecrosis in the femur and humerus than that found in rabbits with either Shwartzman reaction or steroid injection alone. Osteonecrosis was observed in several foci that were distributed from the diaphysis to the epiphysis in both bones. Histologically, the bone marrow cells underwent necrosis, whereas the bone trabeculae demonstrated either empty lacunae or pycnotic nuclei of osteocytes. Exogenous steroids appeared to potentiate the Shwartzman reaction and the magnitude of osteonecrosis, perhaps by increasing endothelial damage and hypercoagulability of those intraosseous and extraosseous vessels that subsequently thrombosed. This model may not only be useful in clarifying the etiology and early pathogenesis of human osteonecrosis after corticoid therapy, but also in designing pharmaceuticals for prevention and early treatment.