Blood erythroid progenitors (BFU-E) from patients with sickle and thalassemic syndromes were compared with those from normal individuals. The day of maximal colony formation in methyl cellulose was slightly later in the cultures from the patients with hemoglobinopathies than in the normal cultures. The number of colonies/100,000 mononuclear cells was similar in all cultures on day 13, but was higher in the hemoglobinopathy cultures on the day of maximal growth. The number of BFU-E/mL of blood was significantly higher than normal at all times in both sickle cell anemia and thalassemia. The proportional synthesis ofγglobin was twice normal in all sickle cultures, and 4 times normal in those fromβ+-thalassemia. Hemin and interleukin-3 increased the numbers of erythroid colonies in all cultures, but did not consistently alter the globin synthesis patterns. Each progenitor population has a unique pattern in terms of time course, number of BFU-E, and level ofγglobin synthesis. These features indicate distinct types of BFU-E, or differences in accessory cells, or both, which distinguish blood-borne erythropoiesis in normals and those with hemoglobinopathies.