The ability of circulating progenitor cells to develop erythroid colonies was studied in vitro in the presence or absence of growth factors (5637‐CM and erythropoietin) in 63 patients with sickle cell disease (SCD) (36 homozygotes for hemoglobin [Hb] S, 13 double heterozygotes for Hb S and β thalassemia, and 14 SC patients) in Southeast Brazil. In the presence of growth factors, SCD patients (all genotypes) presented significantly higher numbers of circulating burst‐forming unit‐erythroid (BFU‐E/5 × 10⁵ MNC), when compared with control subjects. However, when the progenitor cells were cultured in the absence of added stimulus, high numbers of BFU‐E were observed only in the genotypes SS and S/β thalassemia. SC patients presented a similar response to the control subjects. Moreover, there was an inverse correlation between spontaneous (without stimulus) BFU‐E and Hb levels in SCD patients. These results suggest that the formation of spontaneous BFU‐E observed in SCD may be due to an expanded erythropoiesis secondary to hemolysis. Am. J. Hematol. 61:40–45, 1999. © 1999 Wiley‐Liss, Inc.