We have previously shown that upper-body adipose tissue is more lipolytically active than lower-body adipose tissue in lean and obese women. The present studies were conducted to determine whether these regional differences are also present in men. Twenty-five lean, healthy men and 24 lean, healthy women underwent measures of body composition, postabsorptive systemic free fatty acid (FFA) flux, and leg and splanchnic FFA uptake and release. Upper-body adipose tissue was more lipolytically active than lower-body adipose tissue in both men (53.4 +/- 32.2 v 26.6 +/- 12.9 micromol x kg fat(-1) x min(-1), P < .001, respectively) and women (41.2 +/- 22.3 v 18.4 +/- 8.2 micromol x kg fat(-1) x min(-1), P < .001, respectively). The correlations between leg FFA release and systemic FFA flux were modest in women and men (r = .38, P = .07 and r = .56, P = .003, respectively) as were the correlations between splanchnic FFA release and systemic FFA flux (r = .41, P = .06 and r = .40, P = .07, respectively). No effect of gender on the relationship between leg or splanchnic FFA release and systemic FFA flux was detected. In summary, upper-body FFA release is greater than lower-body FFA release in both men and women, and the relationship between leg or splanchnic FFA release and systemic FFA release is weak and similar in men and women. These findings suggest that regional differences in postabsorptive FFA kinetics are unlikely to be responsible for differences in regional fat distribution.