The objective of the present study was to gain a better understanding of the role played by scarce leptin production in the deranged sexual development observed in patients with thalassemia. We studied 101 patients at different stages of puberty. Patients of both sexes were divided into three groups according to Tanner stages: T1-2 (20 males and 12 females), T3-4 (9 males and 4 females) and T5 (48 males and 8 females). Serum levels of leptin, ferritin, testosterone and estradiol were assessed. Leptin levels were adjusted for body mass index (BMI) using reference ranges stratified on the basis of gender and pubertal development. Deviations from the mean reference values were evaluated by calculating the standard deviation scores. Mean leptin standard deviation scores were significantly lower than expected in pubertal stage T1-2 and T3-4 in males and T3-4 and T5 in females. The peak leptin level was delayed in boys (13 years). In girls, parallelism between leptin and BMI was present until age 7-10 years; thereafter, although BMI constantly increased, leptin levels fell dramatically. Mean ferritin levels were significantly higher in pubertal stage T1-2 among males and in T5 among females. These findings show that in thalassemia adipose tissue is unable to assure adequate leptin production just when the highest leptin secretion is required and suggest that this inappropriate leptin secretion may be a cofactor of the derangement in pubertal timing observed in patients with thalassemia.