BACKGROUND Proteoglycan (PG)-LDL interaction is likely to be involved in lipid deposition in arterial wall. The relative content and the structural properties of different PG populations change in human aorta with atherosclerotic degeneration. Therefore, we extracted and separated these PGs from human aorta samples with increasing severity of atherosclerotic involvement and studied their interactions with human LDL. METHODS PGs were extracted with 6 M urea, purified by ion-exchange chromatography and separated into two different populations (PGI and PGII) on the basis of hydrodynamic size and glycosaminoglycan composition. The interaction of both PGI and PGII with LDL was studied separately by precipitation assay. RESULTS The ratio PGI/PGII decreased markedly with increasing severity of the disease. Both PGI and PGII formed insoluble complexes with LDL. However, the shape of saturation curves was markedly different. An excess of PGI from normal or intermediately affected aorta inhibited insoluble complex formation with LDL. On the contrary, an excess either of PGII or of PGI from severely affected aorta did not inhibit insoluble complex formation. In the case of PGII, the maximum of percentage cholesterol precipitated was higher when PGII from severely affected aorta was used. CONCLUSIONS The different interactions of LDL with either PGI or PGII are likely to depend on the different structural properties of PGs. The decrease of PGI/PGII ratio following atherosclerotic degeneration could play an important role in lipid deposition in arterial wall.