To examine if postprandial splanchnic/hepatic free fatty acid (FFA) delivery is increased in upper-body (UB) obesity, and to determine the adipose tissue depots responsible for the greater postprandial FFA availability, we measured systemic and regional uptake and release of FFAs ([1-(14)C]palmitate) before and during a 5-h frequent-feeding mixed meal in eight UB and eight lower-body (LB) obese women. Postabsorptive FFA flux and splanchnic FFA delivery were not different in UB and LB obese women; however, postprandial FFA concentrations (257 +/- 45 vs. 81 +/- 12 micromol/l, P < 0.0001), FFA flux (8.5 +/- 1.2 vs. 3.9 +/- 0.8 micromol x kg(-1) fat-free mass x min(-1), P < 0.0001), splanchnic FFA delivery (275 +/- 45 vs. 88 +/- 24 micromol/min, respectively, P < 0.005), and estimated hepatic FFA delivery were greater in UB than LB obese women. Nonsplanchnic UB adipose tissue FFA release was greater in UB than in LB obese women (276 +/- 71 vs. 97 +/- 37 micromol/min, respectively, P < 0.05) and accounted for the greater postprandial FFA availability in UB obesity. Postprandial leg glucose uptake was less in UB than in LB obese women (8.4 +/- 5.1 vs. 22.9 +/- 2.6 micromol x kg(-1) leg fat-free mass x min(-1), P < 0.05). We conclude that the elevated postprandial FFA release observed in UB obese women originates from the nonsplanchnic UB fat, not visceral fat. These results suggest that visceral fat may be a marker for, but not the source of, excess postprandial FFAs in obesity.