The relative safety of 3 percent Dextran 40-electrolyte solution alone as replacement fluid during plasma exchange is described. Using an automated blood cell separator, the authors exchanged 3.21 of plasma 64 times in 11 patients with paraproteinemia secondary either to Waldenström's macroglobulinemia or multiple myeloma (malignant paraproteinemia). Then they replaced the plasma with an equal volume of 3 percent Dextran 40-electrolyte solution. They administered no protein-containing solutions during or after the plasma exchanges. Despite marked hypoalbuminemia immediately after plasma exchange, the plasma colloid osmotic pressure level fell only slightly because of the high concentration of plasma low-molecular dextran. The hemostatic abnormalities were similar to those seen in patients whose plasma was replaced with albumin solution. The exchanges were tolerated well clinically and no serious complications occurred during or after exchange. The authors believe that the 3 percent Dextran 40-electrolyte solution can be used safely as the sole replacement fluid in intensive plasma exchange programs for patients with malignant paraproteinemia.