The technique of cryofiltration has been applied in the treatment of cryoglobulinemia. Good clinical improvement has been demonstrated accompanied by decreases of cryoglobulin levels. Three treatments in a week produced transient improvement of clinical symptoms and reduction of cryoglobulin levels. Follow-up treatments performed at adequate frequency and volume processed maintained relief of symptoms and serologic improvement. The cryofilter demonstrates good selectivity for cryoglobulin removal in cryogel, confirmed by electrophoretic analysis of both the cryogel filtrate from the cryofilter used clinically. Plasma cryofiltration appears to be a safe alternative to plasma exchange, requiring no replacement fluids.