We measured red cell parameters during recombinant human erythropoietin (rHuEPO) therapy associated with appropriate iron supplementation in chronic hemodialysis patients. Increased erythropoietic activity led to a bias in red cell parameter determination. The percentage of hypochromic red blood cells, usually used as the most effective predictor of response to iron supplementation, increased following the appearance of a younger red cell population since the same Hb content in these younger, larger cells gives a lower Hb concentration.