Hormone replacement therapy (HRT) prevents bone loss in postmenopausal women, but some women are resistant to therapy. A recently reported case of severe estrogen resistance caused by a germline mutation at the estrogen receptor (ER) gene locus suggests the possibility that other variants of the ER gene could be responsible for resistance to HRT and could also be an answer to the heritable components of bone density. Three restriction fragment length polymorphisms (RFLPs) at the ER gene locus, represented as BstUI (or B variant), PvuII, and XbaI, and their relationship to bone mineral density (BMD) and estrogen responsiveness to HRT were examined in 248 healthy postmenopausal women, aged 41-68 yr (mean +/- SD, 52.0 +/- 4.6 yr) in Korea. The BstUI restriction site was not found in Korean women. The distribution of the PvuII and XbaI RFLPs was as follows: PP, 35 (14.1%); Pp, 136 (54.8%); pp, 77 (31.1%) and XX, 18 (7.3%); Xx, 72 (29.0%); and xx, 158 (63.7%), respectively (capital letters signify the absence of and lower case letters signify the presence of the restriction site of each RFLP). There was no significant relation between ER genotypes and z score values of lumbar spine BMD. Also, no significant genotypic differences were found in the change in lumbar spine BMD and those in biochemical markers before and after 1 yr of HRT. These data indicate no significant effects of ER genotypes on BMD and estrogen responsiveness after HRT.