Various LDL-apheresis systems have gained wider clinical acceptance in recent years to treat patients with severe familial hypercholesterolaemia, in particular in patients with coronary artery disease. For each single device data on efficacy have been provided, but up to now no comparative analysis including the novel direct adsorption of lipoproteins from whole blood has been reported. This prospectively designed cross-over comparison of three commercially available LDL-apheresis systems (immunoadsorption, IMAL; dextran sulphate adsorption, DSA; direct adsorption of lipoproteins, DALI) was performed in eight patients with homozygous (n = 3) and heterozygous (n = 5) familial hypercholesterolaemia. Removal of atherogenic lipoproteins was highly effective in all systems, for LDL-cholesterol in particular: DSA: - 84.3 +/- 6.2%; IMAL: -82.1 +/- 8.3%; DALI: -76.6 +/- 7.2% (P < 0.05 as compared DALI versus IMAL and DSA). A reduction in Lp(a) of about 63% was achieved by each device. Loss in HDL-cholesterol was highest with IMAL (-21.3 +/- 4.9%, P < 0.05) as compared to the other two treatment modalities. DSA decreased HDL-cholesterol by - 10.4 +/- 6.1% and the DALI system by -12.7 +/- 5.0%. Remarkable differences were found for the removal of fibrinogen (DSA: -29.8 +/- 14.7%, (P < 0.05 versus DALI/IMAL); IMAL: -21.4 +/- 10.1% (P < 0.05 versus DALI); DALI: -14.8 +/- 8.0%). The shortest duration for treatment was achieved by the DALI system (135 +/- 20 min, P < 0.05 versus IMAL (195 +/- 20 min) and DSA (187 +/- 29 min)). No side effects were recorded in the total of 96 treatments performed during the study. Long-term observations have yet to prove whether these differences in efficacy may be of clinical relevance.