Comparison of the effects of plasma exchange using llpoproteln-deflclent plasma with those of LDL apheresis using a dextran sulphate column was undertaken In two groups of Watanabe heritable hyperlipidemic rabbits pre-labelled with 3 H-cholesterol. Total and HDL cholesterol were reduced more by plasma exchange but HDL cholesterol rebounded higher after LDL apheresis; rises In HDL cholesterol correlated with preceding decreases In both HDL and total cholesterol. An Increase In the specific activity of HDL cholesterol occurred on the day after each procedure, being more marked after plasma exchange, and was accompanied by a decrease In the cholesterol/phosphollpld ratio of HDL. These results suggest that an Influx of extravascular HDL Into plasma occurred after both procedures, resulting In mobilization of tissue cholesterol. (Arteriosclerosis 7:256-261, May/June 1987) P lasma exchange, which was first introduced over 10 years ago to treat homozygous familial hypercholesterolemia (FH), results in gradual regression of cutaneous and tendon xanthomata.12 Indirect evidence that this reflects mobilization of tissue cholesterol was obtained by pre-labelling patients' tissues with radioactive cholesterol and demonstrating acute rises in the specific activity of plasma cholesterol after plasma exchange.1 In one instance analysis of individual lipoproteins showed this rise to be localized to high density lipoprotein (HDL) cholesterol. 3 An Inverse relationship between the concentrations of HDL cholesterol in plasma and the size of the exchangeable pool(s) of tissue cholesterol has been proposed 4 and the possible role of HDL in transporting cholesterol from tissues into plasma was reviewed recently.5 Several, 6 " 8 but not all, 9 epidemiological surveys have shown an increased risk of developing coronary heart disease (CHD) in those with low HDL cholesterol levels, and angiographic data suggest that HDL cholesterol is inversely correlated with the severity of coronary arterial lesions, 10 ' 11 as well as with the likelihood that these will progress. 12 -13 In the light of these findings and because plasma exchange removes HDL as well as low density lipoprotein (LDL), techniques designed to conserve HDL during LDL removal have been developed. These include exposing whole blood to heparin-agarose beads 14 removes LDL but not HDL, a process known collectively as LDL apheresis. The present study compares the effects of plasma exchange and LDL apheresis in Watanabe heritable hyperiipldemic (WHHL) rabbits, an animal model of FH.