AbstractAn on‐line continuous system for the selective precipitation of low‐density lipoproteins (LDL) and very low‐density lipoproteins (VLDL) has been devised and tested. This system conserves high‐density lipoproteins (HDL) and other plasma macromolecules. LDL and VLDL are precipitated from plasma using 10–35 mg/dl dextran sulfate (Mr5,000) in the presence of 55 mM calcium with a reduced concentration of monovalent cations. The plasma is obtained by membrane filtration of whole Wood using the COBE Gentryr̀ TPE System (Cobe Laboratories Inc, Lakewood, Co.). The precipitated LDL plus VLDL is removed by filtration, and the electrolytes are restored by dialysis. The plasma minus LDL plus VLDL is then returned to the patient.Four patients with heterozygous familial hypercholesterolemia (type II) were treated 70 times. The mean pretreatment serum cholesterol was 383 mg/dl. The mean reductions in plasma components were: LDL plus VLDL 63%; HDL 27%; fibrinogen 19%; albumin 15%; IgG 20%; IgA 19%; IgM 25%; C3 30%; and C4 27%. The cholesterol returned to near normal values in approximately 2 weeks after each treatment.Four normal volunteers were each treated one time. These individuals had a mean pretreatment serum cholesterol of 201 mg/dl. The mean reduction in plasma components were: LDL plus VLDL 70%; HDL 27%; fibrinogen 24%; albumin 14%; IgG 18%; IgA 17%; IgM 20%; C3 27%; C4 22%; C3 proactivator 12%; alpha1‐antitrypsin 17%; ceruloplasma 17%; transferin 18%; alpha2‐macroglobulin 17%; and orosomucoid 13%.It is our conclusion that dextran sulfate precipitation is an effective on‐line means of selectively removing LDL plus VLDL from plasma while conserving HDL and other plasma macromolecules. The capacity of the system is limited only to the size of the filter (currently estimated at over 30 gm of cholesterol). The reduction of LDL plus VLDL is limited only by the quantity of plasma processed while the reduction in the other plasma components is virtually independent of plasma