Individuals with homozygous beta-thalassemia are either severely anemic or dependent on blood transfusion to sustain life. Deficient synthesis of the beta chain leads to imbalanced chain synthesis with an excess of alpha globin. This alpha globin precipitates, causing ineffective erythropoiesis and shortened red cell survival. In patients with homozygous beta-thalassemia, enhanced gamma globin synthesis could partially compensate for the deficient synthesis of beta globin rendering chain synthesis more balanced and reducing the relative excess of alpha chains. The purpose of this protocol is to test the hypothesis that induction therapy with 5-azacytidine, followed by maintenance treatment with oral phenylbutyrate will enhance gamma globin synthesis, increase red cell production and partially or substantially correct the anemia in patients with homozygous beta-thalassemia.