Of 44 male patients with idiopathic hemochromatosis who were diagnosed at an early stage without morphological or biochemical evidence of liver disease, 25% suffered from impotence and 34% manifested glucose intolerance. Impotence was correlated with a 50% reduction in plasma testosterone, resulting from a 63% decrease in testosterone production. Testicular atrophy was caused by insufficient secretion of gonadotropins due to the selective accumulation of iron in gonadotropic cells of the pituitary gland. However, peripheral sexual hormone metabolism, in particular the conversion of androgens to estrogens, remained unaltered. It was therefore possible to employ substitution therapy successfully with testosterone in these men, and hyperestrogenism was not observed as a side effect. The pathogenetic factors in the development of diabetes mellitus in patients with idiopathic hemochromatosis include impaired insulin secretion caused by the selective deposition of iron in B-cells of the pancreas and insulin resistance due to iron accumulation in the liver. In particular, the insulin resistance is markedly improved after depletion of body iron stores by phlebotomy treatment, resulting in lower insulin requirements in patients with insulin-dependent diabetes as well as improvement of carbohydrate metabolisms in about half of the patients with non-insulin-dependent diabetes. We have concluded that hypogonadism and carbohydrate intolerance are caused by the specific distribution pattern of excess iron in the organism, accompanied by functional impairment of affected parenchymal cells.