The efficacy of subcutaneous recombinant human erythropoietin (rhEPO) (500 U/kg; administered twice a week during the 3 weeks before surgery) in the recovery of preoperative hemoglobin concentrations within a 3- week period was studied in 40 patients, each of whom donated 2 units (900 mL) of blood for their own use before total hip replacement surgery. Twenty autologous blood donors received rhEPO (EPO group) and 20 were not treated (control group). The initial hemoglobin concentration (14.0 ± 1.0 g/dL [140 ± 10 g/L]) was completely recovered before surgery (14.0 ± 1.6 g/dL [140 ± 16 g/L]) in the EPO group, while a decrease from 13.8 ± 1.1 to 12.2 ± 1.3 g per dL (138 ± 11 to 122 ± 13 g/L) was observed in the control group. The preoperative reticulocyte count showed more than sixfold increase in the EPO group, whereas a twofold to threefold increase was found in the control group. Serum ferritin concentration fell to 42 ± 29 micrograms per L in the EPO group and to 54 ± 35 micrograms per L in the control group. The postoperative serum erythropoietin concentration in the EPO group was significantly lower than that in the control group, but it did not differ from the pretreatment value and was attended by a higher hemoglobin concentration after surgery. Only transient flu-like symptoms were mentioned by patients who were treated with rhEPO. Changes in blood pressure or platelet count or other adverse events were not observed. This study demonstrates that subcutaneous rhEPO is safe and effective for the complete correction of the loss of 2 units of blood within a 3-week period.