A dose-finding study of recombinant human erythropoietin (rhEPO) was performed in 60 autologous donors who donated 2 units of blood prior to orthopaedic or vascular surgery. The correction of phlebotomy-induced anaemia was studied in four groups of 15 patients who received 500 U/kg, 250 U/kg, 125 U/kg or no (controls) rhEPO subcutaneously twice per week during a 3-week period. Haemoglobin concentration in the 500 U/kg, 250 U/kg and 125 U/kg group and in the controls reached respectively 99.2, 98.8, 91.9 and 87.1% of pre-phlebotomy value. Flow cytometric analysis of reticulocytes showed a steady increase of reticulocyte count as the dose increased. Maximal levels of high fluorescence reticulocytes which represent early changes of erythropoiesis were reached after 7 d and decreased thereafter in each group. Serum ferritin decreased significantly to approximately 50% of baseline values in all groups; no differences in the decrease of serum ferritin were observed between the patients who received rhEPO and the controls. No severe adverse events were observed. This study demonstrates a dose-related effect of rhEPO on erythropoiesis in autologous donors during the first 2 weeks. No further increase of reticulocytes was observed despite continued rhEPO therapy, which may be due to the inability of the mononuclear phagocytic system to release additional iron. To restore pre-phlebotomy haemoglobin concentration, a dose of 250 U/kg rhEPO was sufficient.