Five, repeatedly transfused, patients with refractory anemia (RA) or RA with ringed sideroblast (RARS) subtypes of myelodysplastic syndrome (MDS), with serum ferritin (SF) levels of > 2,000 microg/L, and one female with Hb E [beta26(B8)Glu --> Lys]/beta0-thalassemia (thal) with an SF level of 1,760 microg/ L, were treated with deferiprone (L1) at the dose of 4-6 g per day for at least 26 months. Beginning in the second month, all patients received recombinant human erythropoietin (rHuEPO) at the dose of 150 IU/kg thrice weekly, subcutaneously for 24 months. A significant increase in iron excretion after combined administration of L1 and rHuEPO compared to treatment with L1 as a single agent, was observed in all patients. The amount of excreted iron in urine ranged from 7.5 to almost 20 mg per day. In one patient, a response to rHuEPO resulted in transfusion independence and her SF decreased from 2086 to 879 microg/L. In four MDS patients, who remained dependent on red blood cell (RBC) transfusions, simultaneous administration of L1 and rHuEPO enabled the stabilization of SF levels, despite continuing iron load from the transfusions. Combined administration of rHuEPO and oral iron chelators may potentiate mobilization of storage iron and maintain iron balance in transfusion-dependent iron overloaded early MDS patients.