Epidemiological studies indicate low incidence of endometrial cancer in oriental countries with soy based diet. Isoflavones and flavones present in soybean have been shown to be anti-proliferative agents. Some of the isoflavones have been shown to inhibit tyrosine protein kinase (TPK) activity. Effect of these compounds on endometrial cancer cells has not been fully investigated. The purpose of our present study is to investigate (1) the effect of different phytoestrogens on the growth of endometrial cancer cells (HEC-1-A) in culture and (2) the effect of these compounds on the proliferative action of insulin, which is a tyrosine kinase dependent phenomenon. Isoflavones genistein, diadzein, biochanin A and a flavone apigenin were studied. The effect of these agents on cell growth was investigated by monitoring cell number and incorporation of 3 H-thymidine into the DNA of the cells. All the four compounds studied, produced dose dependent inhibition of cell growth. The potency of these isoflavones on cell growth inhibition was genistein > apigenin > biochanin-A > diadzein. At the concentration of 10 - 5 M, cell growth was inhibited to 27% by genistein, 37% by apigenin, 42% by biochanin-A and 77% by diadzein. Addition of 100 ng/ml of insulin, after 24 h culture in serum free medium, resulted in an increase in 3 H-thymidine incorporation and cell number. Genistein, apigenin and biochanin-A partially blocked this increase, while diadzein had no effect. These results indicate that (1) genistein is the most potent inhibitor of growth of endometrial cancer cells, (2) anti-proliferative activity of genistein, apigenin and biochanin A could be due to inhibition of TPK of growth factor receptors, (3) diadzein does not inhibit insulin induced TPK activity, and (4) Isoflavones and flavones in soydiet may offer protection against endometrial cancer.