The present paper evaluates the variations of the hypothalamo-pituitary gonadal axis during Danazol treatment in pubertal boys with marked gynecomastia (breast size more than 6 cm in diameter). Before treatment a normal sleep-dependent gonadotropin increase was found together with a normal response to LHRH stimulation. Plasma prolactin increased at sleep as well. Plasma testosterone values were normal for pubertal age. During Danazol treatment 200 mg daily for 6 months basal gonadotropin levels, the sleep related hormone increases as well as the response to luteinizing-hormone releasing hormone (LHRH) stimulation were blunted. Concomitantly, testosterone values decreased to values seen in pubertal stage II-III. After 6 months of therapy, 4 of 5 boys treated so far, demonstrated a reduction of the gynecomastia to a maximum of 3 cm in diameter. In 1 boy Danazol treatment was finished after 3 months. Because of increased psychological problems a mastectomy was performed. 6 months after cessation of Danazol treatment a normal sleep dependent gonadotropin rhythm and a normal response to LHRH was found again demonstrating a normalization of the physiologic sleep-related gonadotropin rhythms. Plasma testosterone levels nearly increased to values seen before treatment. From the clinical aspect there were no signs of a recurrence of the marked pubertal gynecomastia in all boys treated with Danazol. These results indicate that Danazol is a specific gonadotropin inhibitor acting at the hypothalamo-pituitary level. No side effects on other hormones or on the development of secondary sex characteristics were noted during and after Danazol treatment.