These studies were conducted to determine whether men and women differ with regards to their overnight postabsorptive (basal) and postprandial fatty acid kinetics. Systemic oleate turnover ([9,10(3)H]oleate) was measured before and after the consumption of a mixed meal. Leg and splanchnic free fatty acid (FFA) uptake and release were measured, allowing the calculation of upper-body subcutaneous FFA release. RESULTS: basal oleate flux was virtually identical in men and women (3.0 +/- 3 versus 2.9 +/- 0.4 mumol.kg FFM-1.min-1), however, oleate Ra suppressed more in women than in men following meal ingestion (0.5 +/- 0.1 versus 0.8 +/- 0.1 mumol.kg FFM-1.min-1, P < 0.05). The fractional contribution of basal, regional FFA release to total FFA flux was not significantly different between men and women. In contrast, oleate release by upper-body subcutaneous adipose tissue was significantly greater (30 +/- 5 vs 8 +/- 3 mumol/min, respectively, P < 0.01) in men than in women during the meal nadir of FFA flux, whereas splanchnic oleate release was a greater percentage (39 +/- 7% vs 20 +/- 3%, respectively, P < 0.05) of nadir oleate Ra in women than in men. Thus, normal weight men and women differ significantly in the postprandial regulation of adipose tissue lipolysis in that men's upper-body subcutaneous adipose tissue is more resistant to the antilipolytic effects of meal ingestion. Differential regulation of regional adipose tissue lipolysis could contribute to the gender based differences in body fat distribution.