Two patients with Waldenström's macroglobulinemia (WM), which had become resistant to cytotoxic drugs, were treated for features of the hyperviscosity syndrome by repeated plasma exchange with the continuous-flow blood-cell separator over periods of 36 and 28 months, respectively. After four initial weekly plasma exchanges the procedure was carried out every 4 to 6 weeks and both patients tolerated it well. Relative viscosity of the serum was maintained within the normal range in one patient, and both patients remained free of symptoms of the hyperviscosity syndrome. The results suggest that treatment of WM by long-term "maintenance" plasma exchange alone should be considered in any patient with complications due to chemotherapy or whose disease fails to respond to chemotherapy.