Isoflavones are natural plant phytoestrogens which have been shown to have anticancer proliferation, differentiation and chemopreventive effects. In order to determine structure-function requirements, we compared the effects of several isoflavone derivatives and one flavone on mouse erythroleukemia (MEL) cell growth and differentiation. All chemicals tested are closely related in structure to genistein (4',5,7-trihydroxyisoflavone), a known differentiation inducer and tyrosine protein kinase inhibitor. Genistein, daidzein (4',7-dihydroxyisoflavone) and genistin (7-glucoside of genistein) induced differentiation of MEL cells based on benzidine staining. Biochanin A (5,7-dihydroxy-4'-metho-xyisoflavone) and apigenin (4',5,7-trihydroxyflavone) had no differentiation inducing effect. The potency of these chemicals on cell growth inhibition was apigenin > genistein > genistin > biochanin A > daidzein. These results suggest that the isoflavone structure and 4'-hydroxyl group are essential for the differentiation induction effect, whereas trihydroxyl derivatives are good growth inhibitors. Daidzein is a potent differentiation inducer with the least cytotoxic effect.