The role of adiposity in the relationship of insulin to sex hormone-binding globulin (SHBG) concentration was examined in 31 healthy premenopausal women of varying body weight. Fat mass was estimated by hydrostatic weighing. Concentrations of SHBG and testosterone (T) and cumulative insulin response during an oral glucose tolerance test were measured. The cumulative insulin response was inversely related to SHBG (r = -0.56, P less than 0.01). The relationship between SHBG and cumulative insulin response remained significant (r = -0.47, P less than 0.01) after adjusting for fat mass and T. The fat mass correlated significantly with SHBG (r = -0.51, P less than 0.01). The relationship of SHBG to fat mass remained significant after adjusting for T (r = -0.45, P less than 0.01). However, the relationship between fat mass and SHBG was no longer significant (r = -0.34, P greater than 0.05) after adjusting for cumulative insulin response. Hyperinsulinemia may play an important role in the progressive reduction of SHBG observed with increasing adiposity.