Plasma-exchange was used in 10 patients with mixed cryoglobulinemia. The procedure was used as a primary therapeutic tool to reduce cryoglobulin levels, and in combination with prednisone and cytotoxic drugs. The results show that PE alone is detrimental, although it may be an important adjunct to conventional therapy in MCG with progressive deterioration in the clinical condition, and in those patients who do not respond to drug therapy alone. The weak response to PE in MCG may be due to many technical variables, but mainly to the low percentage of circulating cryoglobulins removed.