BACKGROUND: Phytoestrogens are of special interest in prostate cancer research because populations in Asia with a high consumption of phytoestrogens have a lower incidence of the disease than comparable populations in Western countries. METHODS: This case -control study is nested within a large multiethnic cohort in Hawaii and California. Urine samples were analysed for daidzein, genistein, equol, and enterolactone among 249 incident prostate cancer cases and 404 controls matched on age, race/ ethnicity, date/time of specimen collection, and fasting status. RESULTS: The median excretion of daidzein was 0.173 nmol mg À1 creatinine in cases and 0.291 in controls (P ¼ 0.01), and the median excretion of genistein was 0.048 in cases and 0.078 in controls (P ¼ 0.05). An inverse association was seen for daidzein overall (odds ratio for the highest vs lowest quintile ¼ 0.55, 95% confidence interval ¼ 0.31 -0.98, P trend ¼ 0.03) and seemed to apply to localized (P trend ¼ 0.08) as well as advanced or high-grade cancer (P trend ¼ 0.09). This association was consistent across the four ethnic groups examined. Although the relationship was weaker for genistein, the odds ratios and trends were similarly inverse. Urinary excretion of equol and enterolactone was not significantly related to prostate cancer risk. CONCLUSION: Our findings suggest that high intake of isoflavones, as reflected by urinary excretion of daidzein and genistein, may be protective against prostate cancer.