Objective To investigate the relationship between leptin concentrations, gonadotropic hormone concentrations, and body composition during puberty in a Dutch children cohort. Design In a cohort of 98 children, we determined anthropometric measurements, body composition, and concentrations of leptin, FSH, and LH. Results Sex differences were observed from Tanner stage 1 onwards in weight, body fat percentage, and leptin/fat mass ratio. In boys and girls, the relationship between leptin concentrations and FM was weaker at Tanner stage 2 ( R 2 =0.33 and R 2 =0.39; P <0.001), 3 ( R 2 =0.27 and R 2 =0.36; P <0.002), and 4 ( R 2 =0.21 and R 2 =0.28; P <0.03) than at Tanner stage 1 ( R 2 =0.51 and R 2 =0.67; P <0.001) and 5 ( R 2 =0.46 and R 2 =0.78; P <0.01). In girls, a peak in leptin concentrations (8.5±6.0 ng/ml) preceded a peak in LH and FSH concentrations (15.1±3.5 and 5.0±4.5 IU/l). A lead/lag relationship was observed of leptin at Tanner stage 1 to LH and FSH at Tanner stage 2 ( R 2 =0.12, P <0.05 and R 2 =0.18, P <0.05). In boys, there was no peak in leptin, LH, and FSH; additionally, leptin at Tanner stage 3 was related FSH at Tanner stage 4 ( R 2 =0.17, P <0.04). Conclusion In boys and girls during puberty, factors independent of fat mass become (transiently) more important in the regulation of plasma leptin concentrations. Moreover, in girls, leptin is suggested to act as a permissive factor for the onset of puberty, while, in boys, leptin has a different timing and possibly different function.