The effect of oophorectomy and hormone replacement therapy on cortical and trabecular bone mass was assessed in Sprague-Dawley rats. Bone mineral density (BMD) of the femur and the lumbar spine was determined by dual photon absorptiometry 4 months after surgery. Femoral mineral content was also determined. A significant decrease in bone density and in calcium content was observed after surgical castration. Bone mineral loss was prevented by either progesterone or estrogen, while the combination of progesterone and estrogen had no effect on the bone mineral content. The present study suggests the possibility that estrogen-progestin treatment may be less effective than a therapy with estrogen alone, and that further study on the effect of progesterone alone would be worthwhile.