Treatment with ethinyl estradiol or norethindrone reduces the bone-turnover rate and plasma calcium levels in normal postmenopausal women, without affecting the secretion of calcium-regulating hormones. To assess the effect of these sex steroids in patients with primary hyperparathyroidism, we treated postmenopausal women who had hyperparathyroidism with either ethinyl estradiol (n = 6) or norethindrone (n = 11). After three weeks of treatment, the bone-turnover rate declined and plasma calcium fell from a mean (+/- 1 SE) of 2.77 +/- 0.07 mmol per liter (11.1 +/- 0.3 mg per deciliter) to 2.58 +/- 0.05 mmol per liter (10.3 +/- 0.2 mg per deciliter; P less than 0.01) in the group treated with ethinyl estradiol, and from 2.93 +/- 0.08 mmol per liter (11.7 +/- 0.3 mg per deciliter) to 2.84 +/- 0.08 mmol per liter (11.4 +/- 0.3 per deciliter; P less than 0.05) in the patients who received norethindrone. No significant changes in the plasma levels of parathyroid hormone, calcitonin, or calcitriol were observed after the estrogen-induced increases in vitamin D-binding protein had been taken into account. Since the decline in plasma calcium levels did not stimulate secretion of parathyroid hormone, we conclude that treatment with either sex steroid resets the threshold for secretion of parathyroid hormone. Thus, although the reductions in plasma calcium levels were moderate, sex-hormone therapy may be useful in the treatment of mild hyperparathyroidism in postmenopausal women.