Both gender and circulating hormones are known to influence the regional distribution of tissue mass. Two candidate hormonal biomarkers that are receiving increasing attention based on their somatotrophic influences are insulin-like growth factor-I (IGF-I) and leptin for fat-free mass and fat mass, respectively. This study evaluated the arm, trunk, and leg for fat mass, lean soft tissue mass, and bone mineral content (BMC) in a group of agematched men and women and determined their relationship to IGF-I and leptin. Dual energy X-ray absorptiometry assessed total body and regional body composition in 57 men (28.8±0.7 yrs) and 63 women (29.2±1.0 yrs). Blood was drawn via venipuncture and serum was analyzed via immunoassays for total IGF-I, IGF binding proteins (IGFBPs) 2, 3, and 6 and leptin. Men and women were compared for regional tissue mass on both an absolute and relative basis. After ANCOVA adjustment to control for differences in body mass between men and women, the gender differences that persisted (p 0.05) were for lean soft tissue mass of the arm (men: 7.1 kg vs. women: 6.4 kg) and fat mass of the leg (men: 5.3 kg vs. women: 6.8 kg). Men and women had similar (p 0.05) values for fat mass of the arms and trunk and lean soft tissue mass of the legs and trunk. Serum IGF-I and IGFBP-3 correlated (p 0.05) with all measures of BMC (r's ranged from 0.31 to 0.39) and some measures of lean soft tissue mass for women (r = 0.30), but not men. Leptin correlated (p 0.05) similarly for measures of fat mass for both genders (r's ranging from 0.74 to 0.85) and for lean soft tissue mass of the trunk (r = 0.40) and total body (r = 0.32) for men and for the arms in women (r = 0.56). IGFBP's 2 and 6 did not correlate with any body composition measures. Our data demonstrate that after controlling for age and body size, the main phenotypic gender differences in body composition are that men have more of their muscle mass in their arms and women have more of their fat mass in their legs. Also, distinct gender differences exist (i.e., IGF-I correlates in women and leptin correlates in men) between somatotrophic hormones and lean soft tissue mass.