Future advances in dialysis of end-stage renal disease patients may include improvements in therapeutic continuity and patient mobility. Continuous renal replacement therapies could lead to self-contained, mobile and potentially wearable dialysis units. We investigated an experimental, intravenous slow-continuous plasma separation system (IPSS) as a precursor to direct intravenous hemofiltration. An intracorporeal catheter employs asymmetric hollow fibers to separate blood cells from plasma in vivo. The fibers possess a sieving coefficient of 0.7 µm and remove 99.99% of all platelets. In vivo, catheters sustain an average plasma separation flow rate of 3 ml/min over 22 h, sufficient to remove 2 net liters of water from pigs through an extracorporeal hemofilter. Used catheter fibers are relatively free of protein deposition or clots in situ. In vitro studies suggest that human catheters may perform at 3–4 times the rate of porcine catheters. IPSS is proposed for acute fluid removal in CHF patients refractory to diuretics.