Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.