OBJECTIVE Low plasma testosterone levels are associated with hyperinsulinemia and glucose intolerance in men. However, it is unclear whether these abnormalities are related to the concomitant alteration in regional adipose tissue (AT) accumulation associated with reduced androgen levels. RESEARCH DESIGN AND METHODS We measured plasma steroid levels in a sample of 79 men, ranging from lean to obese (aged 29–42 years), for whom an oral glucose tolerance test (OGTT), anthropometrie and computed tomography (CT) measurements of body fatness, and AT distribution were performed. Sex hormone binding globulin (SHBG) and the following steroids were measured after extraction from plasma and chromatography: dehydro-epiandrosterone, androstenedione, androst–5–ene–3β,17β–diol, testosterone, estrone, and estradiol (E2). RESULTS Several significant negative correlations were found between adrenal C19 steroid precursors, testosterone, SHBG, and fasting insulin levels, as well as between plasma glucose and insulin concentrations measured during the OGTT (−0.25 ≤ r ≤ −0.35, 0.05 ≥ P ≥ 0.001). The best steroid correlate of plasma glucose and insulin homeostasis indexes was the E2: testosterone ratio (0.34 ≤ r ≤ 0.42,0.005 ≥ P ≥ 0.001). However, after correction of steroid levels for either fat mass, body mass index (BMI), or visceral AT area, as measured by CT, no significant residual associations were noted between testosterone, adrenal C19 steroid, SHBG, and estrogen levels and indexes of plasma glucose-insulin homeostasis, although the positive association between the E2:testosterone ratio and glucose area remained significant after adjustment for total body fat mass and BMI. Furthermore, 15 pairs of obese subjects, matched for visceral AT area, showing either low or high levels of the steroids studied, did not differ in fasting insulin and postglucose plasma insulin levels or in glucose tolerance. CONCLUSIONS These results suggest that the previously reported relationships between androgen levels and indexes of plasma glucose-insulin homeostasis are mediated, to a large extent, by concomitant alterations in levels of total body fat and visceral AT in men.