This study addresses whether the expected relationship of 15 specified subcutaneous adipose tissue layers (SAT layers) from 1-neck to 15-calf and body fat mass (FM) with leptin was influenced by a weight-loss program. In 30 obese girls (10 prepubertal, 15 pubertal, and 5 late/postpubertal) SAT layers were measured by means of the optical device Lipometer. Fat mass (FM) was estimated indirectly by means of bioelectrical impedance. Leptin and insulin were determined by means of radioimmunoassays. All measurements were performed before (pre) and after (post) 3 weeks of low-caloric diet and physical training. At the beginning of the study, there were significant correlations for all estimates of adiposity and leptin (0.67 to 0.79; P < 0.0001). Five SAT layers from the upper body and the trunk (0.48 to 0.67; P < 0.01) but none from the abdominal region and lower extremities were correlated with leptin. FM together with SAT layers 4-upper back and 8-lower abdomen (negative slope) explained 79% of the variation in pre leptin values (P < 0.0001). The weight-loss program significantly reduced leptin (P < 0.0001), insulin (P = 0.04), estimates of adiposity (P < 0.0001), and SAT layers 4-upper back (P = 0.0006), 11-front thigh, 13-rear thigh, and 14-inner thigh (P between <0.03 and <0.01). Although significant, the reductions in the four SAT layers were small. Estimated fat-free mass was significantly increased after three weeks (P < 0.05). Changes in SAT layers from the upper extremities and from the trunk were inversely correlated to the decrease in leptin (P between <0.05 and <0.001). Initial leptin was the best correlate of the decrease in leptin (adj. R(2) = 0.815; P < 0.0001). However, when only changes in adiposity and insulin were considered in the regression model, changes in insulin contributed to the fall in leptin (adj. R(2) = 0.23; P = 0.004). When changes in SAT layers were added to the model, changes in SAT layers 2-triceps and 10-hip (negative slopes) contributed to the decrease in leptin (adj. R(2) = 0.48; P < 0.0001). After weight loss, correlations between estimates of post adiposity and post leptin (0.40, P = 0.01 to 0.57, P = 0.0005) were lower compared with pre values. SAT layers 4-upper back and 3-biceps contributed independently to post leptin values (adj. R(2) = 0.50; P < 0.0001). It is suggested that fat mass and SAT layers from the upper body are the main determinants of leptin in obese girls before weight loss. The diet and sports intervention program reduced leptin independent of the reduction in adiposity. The distribution of subcutaneous fat might be a stable correlate of circulating leptin after a short-term reduction in energy intake. Am. J. Hum. Biol. 12:803-813, 2000. Copyright 2000 Wiley-Liss, Inc.