Selective adsorption of proteins from a complex mixture onto an affinity support presents a very powerful approach to protein purification. High density lipoprotein (HDL) and low density lipoprotein (LDL) have been removed from plasma by hydrophobic adsorption chromatography using phenyl-Sepharose. Plasma chromatographed on phenyl-Sepharose is depleted of beta-lipoprotein and apolipoproteins A-I, A-II and E. Less than 5% of the initial amounts of cholesterol, triacylglycerol, sphingomyelin, and phosphatidylcholine remain in the plasma. Column elution with propylene glycol permits recovery of apolipoproteins A-I, A-II and E. This procedure should provide a convenient alternative to ultracentrifugal removal of lipoproteins from plasma.