An improved method for plasmapheresis in the rat was designed. The rat was anesthetized with ketamine hydrochloride, and venipuncture of the iliac vein was performed with a 21-ga butterfly infusion set with 12'' of flexible tubing. Six ml of blood were drawn into a heparinized syringe and centrifugated. After the plasma was separated, the rbc were reinfused through the phlebotomy apparatus. This procedure was performed on each rat weekly for 10 wk without apparent harm to the animals. There were no changes in total serum protein and albumin, and body weights in most animals remained constant. This method should prove valuable in studies in which long-term plasmapheresis is indicated.