Puberty is heralded by the appearance of episodic gonadotropin secretion. Men with idiopathic hypogonadotropic hypogonadism have an abnormality in gonadotropin release and do not undergo normal puberty. Since idiopathic hypogonadotropic hypogonadism is thought to represent a disorder of gonadotropin-releasing-hormone (GnRH) secretion, we used long-term low-dose subcutaneous GnRH, administered in an episodic fashion by a portable infusion pump, in an effort to establish a normal adult pattern of gonadotropin secretion in six men. All subjects noted spontaneous erections, nocturnal emissions, and breast tenderness, which were associated with elevations of serum testosterone levels (77±13 ng per deciliter [mean ±S.E.] before therapy vs. 520±182 ng after one month of treatment; P<0.001). Gonadotropin levels rose to normal adult ranges within one week of therapy and to supraphysiologic levels by 14 days. Testis size increased in four patients, and spermatogenesis was achieved in three patients by 43 weeks of therapy. These results suggest that long-term episodic GnRH administration can reverse idiopathic hypogonadotropic hypogonadism. (N Engl J Med. 1982; 307:1237–41.)