Background: There is considerable interest in using continuous venovenous hemofiltration machines for plasma exchange therapy in children. Methods: Retrospective study of 7 patients and 61 plasma exchange treatments using the Baxter/Edwards Lifesciences BM25 machine with commercially available plasma filters (mostly Asahi Plasmaflo). Results: The average total exchange volume was 1.5 times the plasma volume, achieved at a blood flow rate of 100 ml/m2 (3.5 ml/kg/min) and a turnover rate of 25 ml/kg/h over a 3-hour duration. Fifty-six percent of the time, a mean heparin bolus of 29 units/kg resulted in subtherapeutic activated clotting times. Mean heparin infusion rates of 35 units of heparin/kg/h achieved effective anticoagulation. A calcium infusion rate of 0.11 ± 0.05 mmol/kg/h avoided hypocalcemia. One patient experienced the serious complication of membrane reaction. Conclusions: This setup provides a safe approach to plasma exchange in children. A similar method could be implemented in other centers.