Androgen receptor (AR) CAG repeat length (RL) might modify the relationship between endogenous testosterone (T) and depressive symptoms in men on average over age 50 years. We hypothesized that CAG RL modifies the association between T and depressive symptoms in 525 black and 721 white men under age 40 years participating in the CARDIA Male Hormone Study. We assessed cross-sectional associations of quartiles of total and bioavailable T and tertiles of CAG RL with depressive symptoms, defined as Center for Epidemiologic Studies Depression Scale (CES-D) score > or=16, in 1995-1996. The interaction of CAG RL and total T on depressive symptoms was statistically significant for blacks, whites, and both groups combined. In the combined analysis, the odds ratios (OR) (95% confidence intervals (CI)) across the quartiles of total T were 1.00, 0.17 (95% CI=0.07-0.43), 0.31 (95% CI=0.14-0.70), and 0.49 (95% CI=0.22-1.09) for the shortest RL group. The interaction of CAG RL and bioavailable T on depressive symptoms was statistically significant for black men only, and nonsignificant in a combined analysis. For black men in the shortest RL group, the ORs for the quartiles of bioavailable T were 1.00, 0.41 (95% CI=0.16-1.05), 0.10 (95% CI=0.03-0.38), and 0.35 (95% CI=0.14-0.90). In other CAG groups, there were no relationships of total or bioavailable T with depressive symptoms. CAG RL might modify the association between endogenous total and bioavailable T and depressive symptoms in younger black men. Clinical trials assessing the effects of T replacement therapy on depressive symptoms in hypogonadal men should consider including CAG RL in their design and/or analysis.