We have developed a miniaturized semiclosed cardiopulmonary bypass (CPB) circuit incorporating a centrifugal blood pump (TinyPump) with a volume of 5 ml. The current study was undertaken to evaluate the hemolytic performance of the TinyPump in comparison with the BioPump and to investigate the impact of different CPB circuit volumes on hemodilution, coagulation, and the inflammatory response. Twelve 1-week-old piglets (3.4 +/- 0.2 kg) were used. The circuit comprised a centrifugal pump, a membrane oxygenator, and a cardiotomy reservoir. Cardiopulmonary bypass was conducted with mild hypothermia at 150 ml/kg/min for 3 hours. Transfusion was not performed. Priming volume was 68 ml for the circuit with the TinyPump and 111 ml for the circuit with the BioPump. Although the TinyPump required higher speed, plasma free hemoglobin levels after CPB were not different between the groups. After CPB, the TinyPump group had a significantly higher hematocrit (27% +/- 3% vs. 23% +/- 3%) and lower platelet reduction rate, lower thrombin-antithrombin complex levels, and lower interleukin-6 levels. Better lung compliance with less water content was observed in the TinyPump group. The TinyPump maintained CPB with acceptable hemolysis and lower inflammatory responses. This miniaturized CPB circuit may make transfusion-free open heart surgery feasible in neonates and would help to prevent postoperative organ dysfunction.