BACKGROUND: Veno-venous ultrafiltration may benefit patients with acute or chronic circulatory volume overload. Use of conventional systems, however, may be cumbersome, requiring physician placement of a double-lumen central venous catheter and use of a dedicated dialysis technician and apparatus. METHODS: A simplified peripheral ultrafiltration system including a miniaturized disposable circuit was evaluated in patients with volume-overload states. Separate intravenous catheters (16-18 G) for withdrawal and return of blood (blood flow <or= 40 mL/min, ultrafiltrate <or= 500 mL/h) were placed by nonphysician personnel in upper extremity veins. Twenty-five treatments of up to 8 hours were performed in 21 patients. RESULTS: The primary endpoint of greater than 1 L fluid removal in less than 8 hours was achieved in 23 of 25 treatments. On average, 2611 +/- 1002 mL (maximum 3,725 mL) of ultrafiltrate was removed per treatment (treatment period 6:43 +/- 1:47 hours:minutes). Patient weight decreased from 91.9 +/- 17.5 to 89.3 +/- 17.3 kg (P <.0001) after ultrafiltration. No major adverse events occurred. CONCLUSIONS: Rapid removal of extracellular and intravascular fluid volume excess can be safely achieved via peripherally inserted ultrafiltration without the need for central venous catheter placement.