Six patients with idiopathic isolated gonadotropin deficiency (IGD) were treated with 100 µg LH-RH s.c. 3 times daily, leading to subnormal increases of serum gonadotropin (Gn) and testosterone (T) levels, and promoting puberty from stage I to stage II–III of Tanner. S.c. administration of 100 µg of the more potent and longer-lasting analogue 6-D-Leu-10-Des-Gly-ethylamide-LH-RH induced LH and FSH rises after the very first application in these patients for more than 12 h. However, long-term therapy with the analogue (100 µg s.c./day) did not improve hypogonadism. Paradoxically, on daily treatment (8 patients) with 6-D-Leu-10-Des-Gly-ethylamide-LH-RH the FSH serum levels fell after 1 week and the LH levels after 8 weeks of treatment.