OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in patients with type 2 diabetes. Both elevated urinary albumin excretion and low serum concentrations of dehydroepiandrosterone (DHEA) are associated with increased CVD mortality. This raises the possibility of DHEA as a causal intermediate linking urinary albumin excretion to CVD. RESEARCH DESIGN AND METHODS: Relationships of urinary albumin excretion to serum DHEA sulfate (DHEA-S) concentration and to major cardiovascular risk factors, including blood pressure, serum lipid concentration, glycemic control (HbA1c), and BMI, were investigated in 357 consecutive men with type 2 diabetes. RESULTS: Serum DHEA-S concentrations were lower in patients with macroalbuminuria (866.5 +/- 523.8 ng/ml, P <0.0001) and in those with microalbuminuria (1,014.4 +/- 525.3 ng/ml, P=0.0006) than in patients with normoalbuminuria (1,232.6 +/- 542.4 ng/ml). Serum DHEA-S concentration correlated inversely with log (urinary albumin excretion) (r=-0.227, P <0.0001). Multiple regression analysis demonstrated that duration of diabetes (beta=0.147, P=0.0075), HbA1c (beta=0.156, P=0.0048), BMI (beta=0.194, P=0.0007), systolic blood pressure (beta=0.195, P=0.0005), and serum DHEA-S concentration (beta=-0.192, P=0.0010) were independent determinants of log (urinary albumin excretion). CONCLUSIONS: Serum DHEA-S concentration, which correlated inversely with degree of urinary albumin excretion, may contribute to the link between elevated urinary albumin excretion and higher CVD mortality in male patients with type 2 diabetes.