The effect of oöphorectomy and hormone replacement therapy after oöphorectomy on bone mineral in the femur and vertebra of the rat has been studied. Oöphorectomy resulted in osteoporosis of the femur but not of the seventh caudal vertebra. The administration of a progestogen (ethynodiol diacetate 9 microgram/day) apparently prevented loss of bone mineral content of the femur. This was due to increased periosteal bone formation and widening of the femur. An oestrogen (mestranol 0.9 microgram/day) had no significant effect on the femoral osteoporosis but increased bone mineral content of the vertebra. Combined therapy with oestrogen and progestogen had no effect on any parameter of bone mineral content. The preliminary human study indicated that a progestogen may also be as effective as an oestrogen in prevention of post-menopausal bone loss. There was no evidence of reduction of bone resorption (as indicated by urinary hydroxyproline output) by the progestogen and therefore it is postulated that a progestogen might retard bone loss in the post-menopausal era by stimulating bone formation.