BACKGROUND AND OBJECTIVES: The anemia of low-risk myelodysplastic syndromes (MDS), refractory anemia (RA) and RA with ringed sideroblasts (RARS), may respond to treatment with hematopoietic growth factors (GF)); erythropoietin (Epo) +/- granulocyte colony-stimulating factor (G-CSF). The present study was designed to assess whether functional iron deficiency may develop in MDS patients receiving these treatments. DESIGN AND METHODS: Erythrocyte scattergrams from 34 patients with RA and RARS (untreated, transfused, or GF-treated with partial or complete erythroid response) were analyzed with Bayer-Advia equipment. RESULTS: In untreated RARS, the proportion of hypochromic erythrocytes (Hypo-e, median 6.2%, range 1.1-8%) and hypochromic reticulocytes (Hypo-r, median 45%, range 22-48%), as well as mean corpuscular volume (MCV, median 101 fL) were significantly elevated compared to corresponding values in controls. These values increased further after GF-treatment (median 11%, 57%, and 105 fL, respectively), in spite of improved hemoglobin values and adequate body iron stores. The values observed in untreated RA patients largely fell within the normal range, and there was no significant influence of GF treatment. Notably, the hemoglobin content of reticulocytes (MCHr) did not differ between MDS and controls, and was not influenced by GF treatment. INTERPRETATION AND CONCLUSIONS: The red cell population in RARS shows morphological abnormalities in terms of varying but overall increased size, and reduced hemoglobin concentration. The proportion of abnormal cells increases after successful pro-erythroid GF treatment, indicating that GF promote erythroblast survival, and maturation into erythrocytes. Hence, the finding of hypochromic red cells should not routinely be interpreted as a marker for Epo-induced functional iron deficiency in MDS.