Depot iron, ferritin iron, and ferritin protein were measured in 34 liver needle biopsy specimens obtained from patients with primary and secondary iron-loading diseases. The patients were classified as idiopathic hemochromatosis (14), porphyria cutanea tarda (4), and iron-loading anemias (16). With accumulation of depot iron, the amount of liver ferritin protein increased, however, the ratio of ferritin protein to depot iron fell at concentrations of depot iron in excess of 1,000 micrograms per gm of liver. The liver ferritin protein concentration was not influenced by the specific kind of the iron storage disorder. The mean iron content of ferritin molecules increased about 50% in profound iron overload. In low grade iron overload, the bulk of depot iron was present as ferritin; however, in subjects with heavy iron overload, depot iron consisted of approximately equal amounts of hemosiderin (nonferritin iron) and ferritin iron.