Male sexual precocity is defined as the development of secondary sexual characteristics before 9 years of age. It can be classified as gonadotropin-dependent precocious puberty (GnDP) or gonadotropin-independent precocious puberty (GnIP) and sometimes the differential diagnosis between these entities is difficult. To determine whether long-acting GnRH agonists (GnRH-a) are effective in differential diagnosis of male precocious puberty, we measured gonadotropins and testosterone levels 30 days after a single administration of depot GnRH-a (triptorelin, gosereline or leuprolide) in 10 boys with sexual precocity of different etiologies. Testosterone levels 30 days after depot GnRH-a were in the prepubertal range in patients with GnDP but not in GnIP. We conclude that measurement of testosterone levels 30 days after long-acting GnRH-a is effective in the differential diagnosis of male sexual precocity.