BACKGROUND Alternative medicines are frequently used by patients with breast cancer for general health benefits. American ginseng, an herbal remedy, purportedly alleviates treatment-induced postmenopausal symptoms. METHODS Estrogenic potential of American ginseng root extract to induce the expression of pS2, an estrogen-regulated gene, was evaluated in breast cancer cell lines MCF-7, T-47D, and BT-20 by Northern and Western blot analysis. Competitive studies were performed with ginseng in combination with tamoxifen. Cell proliferation assays were performed using the tetrazolium dye procedure and direct cell count. RESULTS Ginseng and estradiol induce the expression of pS2 RNA and protein in MCF-7 cells, whereas tamoxifen suppresses expression. Neither ginseng nor estradiol induced increased pS2 expression in T-47D or BT-20 cell lines. Although estradiol exhibited a proliferative effect and tamoxifen had an inhibitory effect, ginseng demonstrated no significant effect on cell proliferation. CONCLUSIONS The results of this study suggest that ginseng may exhibit estrogenlike effects on estrogen receptor-positive breast cancer cells by inducing pS2 expression and that the effect of ginseng may be mediated in part through the estrogen receptor. Because ginseng does not exhibit a proliferative effect, it may play a protective role against breast cancer rather than serve as a mitogen.