Soybean foods have been suggested to be practical chemopreventives for human urinary tract cancers. Recently, we demonstrated that the co-operative action of isoflavones results in an increased dose-dependent growth inhibition and apoptosis than any single isoflavone compound. This study aimed to examine the potential of HER-2/neu as a biological target for soy isoflavones. The sensitivity of the bladder cancer cell lines (n=7) to the isoflavones was inversely related to the amount of HER-2/neu expressed. By using HER-2/neu transfection experiments, all three stable transfectants showed a significant growth inhibition by the isoflavone mixture at concentrations attainable in normal adult urine. An increased inhibition of tyrosine phosphorylation of proteins immunoprecipitated by HER-2/Neu was observed in the neu-transfectants compared with controls. The results of this study suggest that HER-2/neu may be a practical biochemical target for urinary isoflavones in vivo.