A 23-year-old man with severe sickle cell disease and a chronic non-healing left leg ulcer was entered into a study in which he received hydroxyurea (HU) and recombinant human erythropoietin (r-HuEPO) in order to modify the severity of his disease. HU 20 mg/kg/day effectively prevented vaso-occlusive crises and improved hematological parameters, but the chronic leg ulcer and chronic mild bone pains remained. Six months later, r-HuEPO 600-800 IU/kg subcutaneously was added at weekly intervals. This led to a rapid and complete healing of the chronic leg ulcer, further improvement in hematological parameters and relief from chronic pains. We conclude that treatment with r-HuEPO may provide an effective therapy for chronic leg ulcers in patients with sickle cell disease.