Isoflavonoids are natural plant compounds and possess antitumorigenic properties. Many environmental chemicals have been found to be estrogenic and can enhance tumor growth in estrogen receptor-positive cells. In the present ent study, the effects of genistein, daidzein, biochanin A, formononetin, and equol on the proliferation of estrogen receptor-positive MCF-7 cells induced by synthetic chemicals 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2,2-trichloroethane (o,p'-DDT), 4-nonylphenol (4-NP), and 5-octylphenol (5-OP) Sound in the environment were investigated. Genistein, biochanin A, equal, and to some extent daidzein, but not formononetin, at <10 mu M can enhance the growth of MCF-7 cells in the absence of environmental chemicals. Formononetin was toxic to MCF-7 cells at the tested concentrations, The environmental chemicals 4-NP, 5-OP, and o,p'-DDT and the natural estrogen 17 beta-estradiol at 5, 5 and 10 mu M and 5 nM respectively induced proliferation of MCF-7 cells. In the presence isoflavonoids (>25 mu M), the environmental chemical-induced cell proliferation was inhibited Individually, genistein (IC50 = 25-33 mu M) was the most potent inhibitor against the induced proliferation of MCF-7 cells of the isoflavonoids needed for a 50% suppression of growth induced by 4-NP, 5-OP, and o,p'-DDT. A mixture of isoflavonoids was the most potent inhibitor against the induced proliferation. Estrogen receptor-dependent and -independent pathways could be involved in the inhibitory actions of isoflavonoids. Because it is impossible to have a chemical-free. environment, the in vitro data presented here are of practical importance to develop evolving dietary strategies and tactics against the adverse health effects of environmental chemicals.