Phytoestrogens, especially Yak-kong or soybean-derived isoflavones have been traditionally used as a supplement of estrogen for preventing postmenopausal osteoporosis in oriental folk medicine. In a previous study, we demonstrated that as Yak-kong and soybean increased MG-63 human osteoblastic cell proliferation, the expression of estrogen receptor $alpha;and;beta;(ER;alpha:;ER;eta$) both were increased. However, the increased level of ER $alpha$ is much higher than that of ER$eta$. To determine whether the altered level of ER $alpha$ expression affects Yak-kong or soybean induced MG-63 cell proliferation, we established cell lines stably expressing either ER $alpha$ or antisense ER $alpha$ RNAs. Increased expression of ER a in MG- 63 cells (ER $alpha$-MG63) enhanced Yak-kong or soybean induced proliferation which paralleled with the enhanced expression of IGF-I. Inhibition of ER $alpha$ expression by antisense $ER;alpha;RNAs;(As-ER;alpha-MG63$) caused these cells to insensitize Yak- kong or soybean induced proliferation and IGF-I expression. Furthermore, the comparable effects between Yak-kong and the combined treatment of genistein and daidzein at $0.5;{ imes};10^{-8}M$, which is a concentration of these two isoflavones similar to Yak-kong at 0.001 mg/ml, on cell proliferation and IGF-I expression in $ER;alpha-MG63;or;As-ER;alpha-MG63$ cells demonstrate that ER $alpha$ plays an important, active role in MG-63 cell proliferation induced by phytoestrogens, especially Yak-kong or soybean derived isoflavones.