A double-blind, placebo-controlled study on 21 postmenopausal osteoporotic women was performed in order to assess the effects of 1 year estrogen therapy (Premarin, 1.25 mg/day) on bone mass, intestinal calcium absorption, and mineral metabolism. Bone mineral content (BMC), measured by dual photon absorptiometry on the vertebral bodies and the femoral shaft, increased in both areas, but the changes were more evident at the former site, which is predominantly trabecular (+8.3%, P less than 0.05), than at the latter, which is mainly cortical (+2.6%, P less than 0.05). An improvement of intestinal calcium absorption was also detected at the end of the study (P less than 0.05) in the estrogen-treated group. Parameters of bone metabolism showed a decrease in hydroxyproline/creatinine ratio and osteocalcin, an increase in calcitonin, and no significant changes in parathyroid hormone (PTH) and alkaline phosphatase. Serum 1,25-dihydroxycholecalciferol (1,25(OH)2D3) levels increased after estrogen therapy, whereas 25-hydroxycholecalciferol (25OHD3) remained stable during the study period. Renal 25-hydroxyvitamin D 1 alpha-hydroxylase reserve, assessed by the PTH-stimulation test, showed a more rapid response in producing a 1,25(OH)2D3 peak in the estrogen-treated patients compared with the control subjects. However, estrogens did not induce an absolute improvement in the secretory reserve. This study demonstrates that 1 year treatment with estrogens improves both intestinal calcium absorption and BMC in postmenopausal osteoporotic women. The latter effect appears to be induced by an inhibition of bone resorption, associated to an increased secretion of calcitonin, whereas vitamin D metabolites do not seem to contribute substantially to the mediation of estrogen action on bone.