Osteoporosis is a common disorder in postmenopausal women, which is probably due to decreased ovarian function. Currently, hormone replacement therapy (HRT), involving administration of estrogen and progestogen, is successfully applied to reduce bone resorption. We studied the effect of HRT on 23 postmenopausal women. This consisted of a combination of 17 beta-estradiol and dydrogesterone, on the serum level of 1,25-dihydroxyvitamin D (1,25(OH)2D) after 0, 6, 12, and 24 months. We found mean serum concentrations (+/- SD) of 1,25(OH)2D of 130.5 pmol/liter (46.1), 152.7 pmol/liter (45.1), 170.8 pmol/liter (64.0), and 155.2 pmol/liter (59.7), respectively. The baseline values in these women were found to be significantly lower than those during therapy (P < or = 0.005). No statistically significant differences were observed when comparing the estrogen-only phase with the combined estrogen-progestogen phase. It is concluded that HRT results in an increase in the serum 1,25(OH)2D concentration which lasts for at least 2 years. This increase may partly explain the preventive effect of HRT on osteoporosis. Furthermore, these results suggest that dydrogesterone does not influence the estrogen-induced changes in serum 1,25(OH)2D concentration.