Aim: To study the relationship between circulating androgens (total testosterone [TT], free testosterone [fT] and dihydrotestosterone [DHT]) and high-density lipoprotein cholesterol (HDL-C) in men with and without cardiovascular disease (CVD). Methods: Cross-sectional analyses included 1 661 baseline samples from the Massachusetts Male Aging Study (MMAS), a population-based cohort of men ages 40-70 years. Serum hormones were measured by radioimmunoassay and HDL-C was determined following precipitation of the lower density lipoproteins. CVD was determined by self-report. Analyses were performed using multiple linear regression. Results: TT and HDL-C were positively correlated in the entire sample (r = 0.11, P = 0.0001). After adjusting for confounders, we found this relationship was mostly limited to the 209 men with CVD. Among men with CVD, TT (P = 0.0004), fT (P = 0.0172)and DHT (P = 0.0128) were all positively correlated with HDL-C, whereas in men without CVD only TT correlatedwith HDL-C (P = 0.0099). Conclusion: Our results suggest that if androgens contribute to CVD in middle-aged men, the effect is not related to a suppressive effect of endogenous T on HDL-C.