In the attempt to define the abnormalities responsible for the severe iron overload found in patients with idiopathic hemochromatosis (IH) we analyzed, in 8 patients with IH and in 7 normal subjects, by using specific cDNA probes, the genes coding for the main iron-related proteins, i.e., transferrin, transferrin receptor, as well as H and L subunits of ferritin. In all the patients tested all the probes failed to evidentiate rearranged bands with any of the restriction enzymes employed. These findings suggest the absence of gross structural alterations of the genes examined. The lack of polymorphic sites recognized by the restriction enzymes employed in this study within or around the genes examined does not allow to associate a specific gene with the disease.