We evaluated whole body and regional (subcutaneous abdominal adipose tissue and forearm) norepinephrine (NE) kinetics in seven lean (body mass index 21.3 +/- 0.5 kg/m2) and six upper body obese (body mass index 36.4 +/- 0.4 kg/m2) women who were matched on fat-free mass. NE kinetics were determined by infusing [3H]NE and obtaining blood samples from a radial artery, a deep forearm vein draining mostly skeletal muscle, and an abdominal vein draining subcutaneous abdominal fat. Mean systemic NE spillover tended to be higher in obese (2.82 +/- 0.49 nmol/min) than in lean (2.53 +/- 0.40 nmol/min) subjects, but the differences were not statistically significant. Adipose tissue and forearm NE spillover rates into plasma were greater in lean (0.91 +/- 0.08 pmol. 100 g tissue-1. min-1 and 1.01 +/- 0.09 pmol. 100 ml tissue-1. min-1, respectively) than in obese (0.26 +/- 0.05 pmol. 100 g tissue-1. min-1 and 0.58 +/- 0.11 pmol. 100 ml tissue-1. min-1, respectively) subjects (P < 0.01). These results demonstrate that adipose tissue is an active site for NE metabolism in humans. Adipose tissue NE spillover is considerably lower in obese than in lean women, which may contribute to the lower rate of lipolysis per kilogram of fat mass observed in obesity.