A number of techniques have been proposed for separating lipoproteins according to their physicochemical properties. However, more recent evidence has pointed out that the physicochemically defined lipoproteins such as VLDL, IDL, LDL or HDL are both chemically and metabolically heterogeneous. According to Alaupovic concept, the plasma lipoprotein system consists of a mixture of particles, each of which is characterized by unique apolipoprotein composition. Using enzyme linked differential antibody immunosorbent assay and differential electroimmunoassay, we have discovered that the determination of lipoprotein particle profiles is essential for further clarification of the diagnostic value of measuring apo B and apo A-I. The metabolism of apo B and apo A-I containing lipoprotein particles seems to be affected primarily by their corresponding apolipoprotein composition. Some particular subpopulations of apo B containing lipoprotein particles, such as LpB containing only apo B, LpB:E containing apo B and (a), have been identified as important risk factors for atherosclerosis. We have also recently demonstrated that the protective effect of HDL is due to particles containing apo A-I but not apo A-II (LpA-I), while those containing apo A-I and apo A-II (LpA-I:A-II) have little or no effect. Dyslipoproteinemias are characterized by distinct profiles of apo B containing particles. Abnormalities in apo A-I containing particles distribution are related to the family history of coronary artery disease in young children and could explain differences in age standardized mortality from ischaemic heart diseases in different populations. Moreover hypolipidemic drugs seem to affect discrete apo B and apo A-I particles in a specific manner.