Cryoprecipitable proteins (CPP), purified from plasmas removed during plasmapheresis treatment of patients with type I1 and type I11 cryoglobulinemia (CG), were evaluated in vitro for their effect on normal leukocyte function. CPP reduced normal mononuclear cell blastogenesis and polyrnorphonuclear cell phagocytosis responses in a dosedependent fashion. At the maximum concentration studied, 5,000 pgiml, CPP were shown to suppress normal blastogenesis and phagocytosis 3 W % and 5040% below the albumin control, respectively. A 50% suppression of normal blastogenesis and phagocytosis was observed at 500 pgiml for type 111 CPP. Leukocyte functions in CG patients were evaluated and compared to those of healthy controls. Blastogenesis and phagocytosis were significantly inhibited in CG patients. These studies suggest that CG patients have defective leukocyte function and that CPP have suppressive effects on normal leukocyte function. Our studies suggest that removal of CPP in CG patients may prove beneficial not only in reducing typical symptoms of CG but also in reducing the potencial inhibitory effects of CPP on leukocyte function.