Previous studies have shown that the mean serum concentration of 1,25-dihydroxyvitamin D [1,25-(OH)2D] is lower than normal in patients with postmenopausal osteoporosis. We studied the mechanism of this abnormality in 12 women with postmenopausal osteoporosis and 10 age-comparable normal women. Parathyroid extract (200 U, twice daily for 3 days) was administered to stimulate the enzymatic conversion of 25-hydroxyvitamin D (25OHD) to 1,25-(OH)2D. The serum concentration of 1,25-(OH)2D was lower (P less than 0.05) at a baseline determination in the osteoporotic subjects than in the normal women and increased significantly (P less than 0.001) above basal values after the administration of parathyroid extract in both groups; however, the degrees of increase in the control and osteoporotic subjects were similar. We conclude, at least under the conditions of our study, that 25OHD 1 alpha-hydroxylase is normally responsive to parathyroid hormone in postmenopausal osteoporosis. Thus, the apparently impaired metabolism of 25OHD to 1,25-(OH)2D appears to be secondary to a decrease in factors that abnormally stimulate 25OHD 1 alpha-hydroxylase activity rather than a primary defect in enzyme reserve capacity.