Increased bone loss in estrogen-deficient normal and osteoporotic postmenopausal women may be due mainly to increased sensitivity of bone-resorbing cells to circulating PTH, but this is supported only by indirect data. Therefore, we tested the responsiveness of bone to PTH directly by using a 3-day iv infusion of bovine PTH-(l-34) at 400 U/day in 9 normal premenopausal women, 10 normal postmenopausal women, and 12 osteoporotic postmenopausal women. Serum calcium and urinary hydroxyproline concentrations increased (P < 0.001) over baseline values during infusion, but the mean increases in both variables did not differ among groups. The data do not support the hypothesis that estrogen deficiency increases the sensitivity of bone to PTH or that the sensitivity in osteoporotic women is greater than that in normal postmenopausal women. Within the constraints imposed by the method of testing, we conclude that the additional bone resorption induced by menopause and by osteoporosis may be due to mechanisms that are not due to enhanced responsiveness of bone to PTH.