Five patients with diet and drug resistant familial hypercholesterolemia (FH) (low density lipoprotein [LDL] cholesterol, LDL greater than 230 mg/dl) were treated by LDL apheresis, using dextran sulfate cellulose adsorption (DSC), to prevent coronary heart disease (CHD). After membrane plasma separation, two 150 ml columns of DSC alternately adsorbed LDL, and were regenerated by 4.1% saline. Five patients received 230 treatments with 7 to 14 days intervals over 6 to 30 months. The treated plasma volume per session was 3.8 +/- 0.6 L. Post-apheresis values in percent of pre-apheresis were: total cholesterol, 42%; LDL, 27%; VLDL, 62%; HDL, 96%; triglycerides, 70%; WBC, 115%; platelets, 88%; C3 complement, 78%; fibrinogen, 67%; albumin, 94% (p less than or equal to 0.005 for all values). Safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to nonatherogenic levels of between 150 and 100 mg/dl, whereas high density lipoprotein remained unchanged. Adverse events (hypotension, angina pectoris, technical problems) occurred in six treatments. Long-term treatment of patients with therapy resistant FH by extracorporeal DSC adsorption is effective and safe.