Bone marrow cells from three patients with idiopathic acquired sideroblastic anemia and one with X-linked sideroblastic anemia were simultaneously cultured in plasma clot and methylcellulose cultures in order to evaluate their erythroid colony (CFUE) cloning potential in these two systems. In contrast to normals, sideroblastic anemia bone marrow cells demonstrated a marked ability to form erythropoietin (Epo)-independent CFUE in methylcellulose culture, and were inhibited in their ability to generate CFUE in plasma clot culture even in the presence of Epo. Addition of citrated plasma to methylcellulose cultures inhibited Epo-independent CFUE growth, but not Epo-dependent growth, by both a normal and patients' bone marrow cells. These results demonstrate that bone marrow cells from some patients with sideroblastic anemia can undergo Epo-independent and Epo-dependent CFUE growth in vitro, and that there is a marked difference in CFUE growth depending on the type of clonal culture method used. It is suggested that the culture microenvironment, plasma, and sensitivity to Epo may be contributing factors which allow specific clones of sideroblastic anemia CFUE-forming cells to proliferate in vitro.