Yam (Dioscorea spp.) is a common food in tropical areas and has been shown to improve the status of sex hormone in postmenopausal women. In this study, the estrogenic activity of yam was examined and active compounds were isolated and identified based on ligand-dependent transcriptional activation through estrogen receptors. Ethyl acetate extracts of various species/varieties of yam were found to activate estrogen receptors alpha and beta to various extents. The extract of Dioscorea alata cv. Tainung No. 2 tuber was fractionated by repeated silica gel column chromatography. The active compounds were isolated and purified by preparative HPLC. Based on NMR and mass spectrometry, two new compounds, hydro-Q(9) chromene (1) and gamma-tocopherol-9 (2), together with three known compounds, RRR-alpha-tocopherol (3), coenzyme Q(9) (4), and 1-feruloylglycerol (5), were identified and shown to activate human ERalpha and beta. These results provide basic evidence for the beneficial effect of yam for menopausal women.