We applied an autologous blood predonation protocol using recombinant human erythropoietin in pediatric open-heart surgery. The study included 69 children weighing 8 kg or more. Twice before operation, 8 ml/kg of blood was taken. At each donation, 100 (group 1; n = 20), 200 (group 2; n = 11), or 300 (group 3; n = 13) units/kg of erythropoietin was given subcutaneously. In group 4 (n = 25), 300 units/kg of erythropoietin was given I week prior to the first donation, followed by 300 units/kg given at each donation. No harmful events occurred during the donation period. During the donation period, the patients' hematocrit decreased but the hernatocrit I day after the operation remarried at 32.1 +/- 0.6% and was 33.3 +/- 0.6% 2 weeks later. The decrease in hematocrit was minimal in group 4 (39.0 +/- 0.6% before donation to 37.5 +/- 0.5% before operation) compared with that of the other three groups. Among those who completed the protocol, 58 patients (93.5%) were discharged without homologous blood transfusion. We consider our protocol of autologous blood predonation using erythropoietin to be safe and effective for avoiding homologous blood transfusion in pediatric patients. The early infusion of erythropoietin prior to the first donation minimizes the decrease in hematocrit level before operation.