Ginseng has been recommended to alleviate the menopausal symptoms, which indicates that components of ginseng very likely contain estrogenic activity. We have examined the possibility that a component of Panax ginseng, ginsenoside-Rb1, acts by binding to estrogen receptor. We have investigated the estrogenic activity of ginsenoside-Rb1 in a transient transfection system using estrogen-responsive luciferase plasmids in MCF-7 cells. Ginsenoside-Rb1 activated the transcription of the estrogen-responsive luciferase reporter gene in MCF-7 breast cancer cells at a concentration of 50 microM. Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of ginsenoside-Rb1 is estrogen receptor dependent. Next, we evaluated the ability of ginsenoside-Rb1 to induce the estrogen-responsive gene c-fos by semi-quantitative RT-PCR assays and Western analyses. Ginsenoside-Rb1 increased c-fos both at mRNA and protein levels. However, ginsenoside-Rb1 failed to activate the glucocorticoid receptor, the retinoic acid receptor, or the androgen receptor in CV-1 cells transiently transfected with the corresponding steroid hormone receptors and hormone responsive reporter plasmids. These data support our hypothesis that ginsenoside-Rb1 acts a weak phytoestrogen, presumably by binding and activating the estrogen receptor.