The purpose of the present study was to determine the immunochemical properties of apolipoprotein (apo) B-100 associated with low density lipoprotein (LDL) in relation to lipid and apolipoprotein composition. LDLs were isolated by sequential ultracentrifugation (1.019<rf< 1.050 g/mL) from two healthy volunteers and 21 dyslipidemic patients to obtain heterogeneous samples of LDL. Lipid (free cholesterol, cholesteryl esters, triglycerides, and phospholipids) and apolipoprotein contents (apo B, apo C-III, apo E) were determined in each LDL sample. Immunoreactivities of apo B were tested in solid-phase competitive-binding radioimmunoassays using seven monoclonal anti-LDL antibodies that reacted with defined epitopes of apo B-100. The relation between lipid and/or protein variables and the immunoreactivity of apo B was evaluated by successive use of Spearman's rank simple correlation, partial correlation, and canonical correlation analyses. The canonical correlation analysis showed that apo B-100 immunoreactivity on LDL is highly dependent on lipid and apolipoprotein composition simultaneously. The results confirmed the influence of surface and core lipids on the expression of the apo B-100 epitopes, independent of their location on the molecule. However, the lipid requirement of LDL strongly influences the expression of epitopes mapped in the LDL receptor-recognition domain. In contrast to apo E, apo C-III does not seem to influence the expression of the apo B-100 epitopes in the LDL range studied. To understand the structural organization (chemical composition and immunoaccessibility) of apo B-100 in LDL and therefore its potential atherogenicity, it is necessary to keep in mind that LDL is an indissociable association of lipids plus apolipoproteins and that both parameters simultaneously act to maintain apo B-100 in its spatial disposition.