The homologous blood prime in cardiopulmonary bypass circuits contributes a significant electrolyte and metabolite load in small infants. The efficacy of hemofiltration and continuous hemodiafiltration of the blood prime in preventing metabolic disturbances in small infants was compared in two groups of 60 patients each. Blood pH, base excess, and calcium concentrations decreased during cardiopulmonary bypass in the hemofiltration group. The acid-base balance was well preserved during cardiopulmonary bypass by continuous hemodiafiltration. This therapeutic strategy may confer an advantage in maintaining more physiological conditions during cardiopulmonary bypass in small infants.