Transfusion therapy now enables children with beta-thalassemia major to reach the second or third decade whereupon they succumb to the sequelae of iron overload. Presumably their life could be extended if iron were removed from their body. Using both the hypertransfused rat and iron rich cultured Chang cells as models of secondary iron overload, we will continue our efforts to identify orally-effective, iron-chelating agents. Oru emphasis will be on multidentate ligands bearing functional groups with a high affinity for iron. We will also attempt to design tissue specific chelators, especially those that might be directed to the heart as cardiac failure is a major cause of death in these patients. Lastly, we will evaluate natural and synthetic polymers as intraluminal chelating agents both to maximize the efficiency of the enterohepatic circulation as a means of removing excess iron from the body and to inhibit the absorption of non-heme from the diet.