Apolipoproteins AIV, B, E, and the Lp(a) glycoprotein are genetically polymorphic in humans. Three common alleles epsilon 2, epsilon 3 and epsilon 4 control the polymorphism of apolipoprotein E. These code for proteins which differ in functional properties, e.g. receptor binding activity and in vivo catabolism. This explains the significant effect of the apoE gene locus on the variability of plasma lipoprotein concentrations and moreover the implication of apoE alleles in the aetiology of multifactorial forms of hyperlipidaemia e.g. familial type III hyperlipidaemia (apoE2; arg158----cys) and polygenic hypercholesterolaemia (apoE4; cys112----arg). A further gene locus controls the concentrations in plasma of the Lp(a) lipoprotein that is composed of an LDL-like particle containing apoB-100 and the disulphide-bonded Lp(a) glycoprotein. The latter exhibits a genetic size polymorphism (MW approximately 400 kD-700 kD) that is controlled by at least seven autosomal alleles. These alleles at the same time are involved in determining the plasma concentrations of the lipoprotein that range from less than 1 mg/dl to greater than 200 mg/dl. Thus there is evidence that genetic variability in apolipoproteins relates to the variability of lipoprotein concentrations in the population and is implicated in the aetiology of multifactorial hyperlipidaemias.