The changes in the red cell and reticulocyte distribution widths during preoperative treatment with recombinant human erythropoietin (rhEPO) were evaluated in a double-blind, placebo-controlled trial in cardiac surgery patients. The increases in the reticulocyte count, in the hemoglobin and in all distribution widths are the expression of the marked preoperative stimulation of erythropoiesis in the patients treated with rhEPO. Only placebo patients with a hemoglobin < or = 7.5 mmol/l or a transferrin > 4.0 g/l at baseline showed an increase in the red cell distribution width or in the reticulocyte hemoglobin distribution width on oral iron therapy alone. While the reticulocyte count and the distribution widths of red cells in the rhEPO patients decreased postoperatively, only the increases in the distribution widths of reticulocytes after the second postoperative day indicate that stimulation oferythropoiesis had taken place. In patients with a low hemoglobin or a high transferrin the rhEPO therapy should be preceded by iron therapy in order to raise the hemoglobin level and reduce the cost of treatment.