Elevation of blood cholesterol, low-density lipoproteins (LDL) and apolipoprotein B (apoB) are hallmarks of familial hypercholesterolemia (FH), a genetic condition caused by the defective functioning of the cellular receptor for apoB-100 in LDL. ApoB-100 is also present in lipoprotein(a) (Lp(a)). In this lipoprotein, apoB-100 is linked to a plasminogen-like protein called apo(a). By direct comparison of the Lp(a) and apoB plasma concentrations in 28 affected and 31 unaffected members of seven families carrying the FH trait and without history of coronary artery disease, we reached the conclusion that LDL receptor activity is not a major determinant of the Lp(a) plasma levels in these subjects. This suggests that the molecular determinants for catabolism of Lp(a) are not the same as those for LDL. Consistent with this view is our observation that the turnover rate of Lp(a) and of LDL apoB, calculated from their rate of reappearance in plasma following Lp(a)/LDL apheresis, differ greatly.