In this study we determined the levels of circulating soluble transferrin receptor (sTfR) in six untransfused and two transfused patients affected by beta-thalassemia intermedia during low-dose rHuEPO administration. While the majority of the untransfused patients showed a temporary increment during the first month of treatment, a higher and enduring increase in sTfR concentration was observed in the two transfused patients until rHuEPO was discontinued. The transfused patients showed a significant increase in the reticulocyte index together with the rise in sTfR and an improvement of the anemia, as evidenced by the decrease in their transfusional requirement. These data suggest that basal erythropoietic activity is one of the main causes of differences in responsiveness to low doses of rHuEPO given in thalassemia intermedia.