In humans, circulating leptin levels are low in early childhood and rise until puberty, whereas the reverse occurs for the soluble leptin receptor (sOB-R). In women, leptin remains high and sOB-R remains low, but in men leptin declines after adolescence and sOB-R increases. These observations suggest that leptin may regulate the production of sOB-R, and that the increased testosterone in adolescent boys may be responsible for the gender differences in leptin and sOB-R. To test this hypothesis, leptin was administered continuously to agonadal juvenile male monkeys for 16 days. No change in sOB-R was observed. Intact juvenile male monkeys were given pulsatile doses of gonadotropins for a period of 7 weeks to induce precocious puberty and assess the effect on plasma testosterone, leptin, and sOB-R. By 4 weeks testosterone had reached adult levels. No changes were observed in leptin, but by week 4, sOB-R was higher than pretreatment values and remained higher at week 7. These data suggest that leptin may not play a significant role in regulating the production of sOB-R and that gender differences in sOB-R in humans may be driven by the increased production of testosterone at puberty in males.