Hormone refractory prostate cancer remains an incurable disease. Newer agents with more activity are required. Genistein is a flavone compound with anti-tumor activity against various tumor systems in vitro. This study is undertaken to assess the efficacy of genistein against hormone refractory prostate cancer. In vitro, genistein appears to be cytotoxic to both the rat prostate cancer cell line MAT-LyLu and the human prostate adenocarcinoma cell line, PC-3. In vivo, however, genistein failed to significantly inhibit the growth of subcutaneously implanted MAT-LyLu cells. More information regarding the pharmacokinetics and bio-availability of genistein is needed to determine if this is an active agent in human metastatic prostate cancer.