Androgens stimulate prostate cancer in vitro and in vivo. However, evidence from epidemiologic studies of an association between circulating levels of androgens and prostate cancer risk has been inconsistent. We investigated the association of serum levels of testosterone, the principal androgen in circulation, and sex hormone-binding globulin (SHBG) with risk in a case-control study nested in cohorts in Finland, Norway and Sweden of 708 men who were diagnosed with prostate cancer after blood collection and among 2,242 men who were not. In conditional logistic regression analyses, modest but significant decreases in risk were seen for increasing levels of total testosterone down to odds ratio for top vs. bottom quintile of 0.80 (95% CI = 0.59–1.06; ptrend = 0.05); for SHBG, the corresponding odds ratio was 0.76 (95% CI = 0.57–1.01; ptrend = 0.07). For free testosterone, calculated from total testosterone and SHBG, a bell-shaped risk pattern was seen with a decrease in odds ratio for top vs. bottom quintile of 0.82 (95% CI = 0.60–1.14; ptrend = 0.44). No support was found for the hypothesis that high levels of circulating androgens within a physiologic range stimulate development and growth of prostate cancer. © 2003 Wiley-Liss, Inc.