The mechanism of impaired calcium absorption in postmenopausal osteoporosis is controversial. If it is caused by calcitriol deficiency, it should be corrected by long term administration of physiological doses of this metabolite, whereas if it is caused by either a primary defect in calcium absorption or intestinal resistance to calcitriol action, it should not be. In 56 osteoporotic women, mean (+/- SE) fractional calcium absorption (0.52 +/- 0.02) was lower (P less than 0.001) than that in 20 age-matched normal women (0.61 +/- 0.02). Treatment with calcitriol (0.5-0.75 micrograms/day) increased calcium absorption after 6-12 months to 0.67 +/- 0.02 (P less than 0.001) and, in 29 patients, to 0.66 +/- 0.02 (P less than 0.001) after 24 months. After treatment, only 1 patient still had subnormal calcium absorption. In 26 patients treated with placebo for 6-12 months, there was no significant change in calcium absorption. For all studies, total calcium absorption (fractional absorption X estimated dietary intake) correlated directly with urinary calcium excretion (r = 0.61; P less than 0.001). Urinary hydroxyproline excretion, an index of bone resorption, was 31.0 +/- 1.5 mg/dl glomerular filtration rate (GFR) initially and decreased during treatment to 24.6 +/- 1.1 mg/dl GFR (P less than 0.001) after 6-12 months and to 27.9 +/- 1.3 mg/dl GFR (P less than 0.01) after 24 months. The finding that calcium absorption can be normalized by small doses of calcitriol supports the hypothesis that insufficient endogenous production of calcitriol is the major cause of decreased calcium absorption in postmenopausal osteoporosis.