To determine the long term effect of estrogen administration upon some biochemical indices of bone formation and resorption as well as serum calcium and phosphorus, the following experiments were carried out. Female rats were divided into the following groups: intact, intact and estrogen-treated, oophorectomized, and oophorectomized and estrogen-treated. Treatment consisted of 400 μg 17β-estradiol/100 g BW twice a week for 1–12 months. Estrogen administration to the intact animals coused no consistent significant changes in any of the parameters measured. It was found that oophorectomy caused a decrease in the serum calcium concentration, a decrease in ash content, an increase in the total hydroxyproline content, an increase in incorporation of [3H]proline into collagen, a decrease in total hexosamine, an increase in the incorporation of [14C]glucose into hexosamine, an increase in the uptake of 45Ca into bone, and an increase in bone collagenolytic activity. The administration of estrogen to the oophorectomized rat corrected the serum calcium changes to normal and returned the decreased ash content, collagen, and hexosamine contents to normal. Estrogen administration only partially reversed the increased uptake of [3H]-proline into collagen and the increased incorporation of [14C]-glucose into hexosamine. The administration of estrogen to oophorectomized animals also returned the 45Ca uptake of bone to normal and caused normalization of the bone collagenolytic activity. The data indicate a sustained decrease in serum calcium and an increase in both bone formation and resorption in the oophorectomized animal. The administration of estrogen largely corrects these abnormalities and the beneficial effects are sustained over a 12-month period.