We measured whole body and regional lipolytic and adipose tissue blood flow (ATBF) sensitivity to epinephrine in 8 lean [body mass index (BMI): 21 ± 1 kg/m²] and 10 upper body obese (UBO) women (BMI: 38 ± 1 kg/m²; waist circumference >100 cm). All subjects underwent a four-stage epinephrine infusion (0.00125, 0.005, 0.0125, and 0.025 μg ⋅ kg fat-free mass⁻¹ ⋅ min⁻¹) plus pancreatic hormonal clamp. Whole body free fatty acid (FFA) and glycerol rates of appearance (R_a) in plasma were determined by stable isotope tracer methodology. Abdominal and femoral subcutaneous adipose tissue lipolytic activity was determined by microdialysis and ¹³³Xe clearance methods. Basal whole body FFA R_a and glycerol R_a were both greater (P < 0.05) in obese (449 ± 31 and 220 ± 12 μmol/min, respectively) compared with lean subjects (323 ± 44 and 167 ± 21 μmol/min, respectively). Epinephrine infusion significantly increased FFA R_a and glycerol R_a in lean (71 ± 21 and 122 ± 52%, respectively; P < 0.05) but not obese subjects (7 ± 6 and 39 ± 10%, respectively; P = not significant). In addition, lipolytic and ATBF sensitivity to epinephrine was blunted in abdominal but not femoral subcutaneous adipose tissue of obese compared with lean subjects. We conclude that whole body lipolytic sensitivity to epinephrine is blunted in women with UBO because of decreased sensitivity in upper body but not lower body subcutaneous adipose tissue.