Because of the central importance of the liver for the metabolism of estrogens and androgens the chronically ill liver per se represents an essential disturbing factor within the hypothalamic-pituitary-gonadal axis caused by the altered hepatic metabolism of the steroid hormones as well as the abnormal synthesis of steroid-hormone-binding proteins with changed free fractions of sex hormones. The question has been differently answered whether a chronic hepatic disease can also be the reason for disturbance on hypothalamic-pituitary and/or testicular level. Recent plasma determination of LH/FSH before and after LHRH and clomiphene, of sex hormones before and after HCG as well as unbound sex hormones in males with chronic hepatic diseases lead to the following conclusion. 1. Chronic liver disease (without idopathic hemochromatosis). Even sever chronic hepatic diseases are not accompanied by primary hypopituitarism. With regard to the impaired Leydig cells stimulation by HCG and the abnormal seminal fluid and testicular histology one can suppose a primary gonadal hypogonadism. However, an additional hypothalamic disturbance has to be considered. 2. Idiopathic hemochromatosis. Presumably in hemochromatosis a primary insufficiency of pituitary and/or testes can take place related to the general metabolic disturbances of this illness. The classic hypothesis of an exclusively primary lesion with secondary hypogonadism does not appear to be correct.