Retention of atherogenic lipoproteins in the arterial intima by extracellular matrix (ECM) is assumed to occur during early atherogenesis and its further development. Low density lipoprotein (LDL) trapped in the intima may undergo oxidative modifications, which initiate a chain reaction in atherogenesis. Lipoprotein lipase (LPL) has been found to mediate the binding of native and oxidized LDL to ECM produced by cultured cells and to contribute to foam cell formation by mildly oxidized LDL. In this study ECM, isolated from human aortic intima with different atherosclerotic lesions, was used for the first time to measure the binding to it in vitro of native and differently oxidized 125I-LDL. Oxidation of 125I-LDL increased its binding to the ECM, which was most prominent with the material isolated from intima at the early stage of atherogenesis. With the progression of atherosclerosis, the ability of the isolated intimal ECM to bind native and oxidized 125I-LDL decreased, and strongly oxidized 125I-LDL decreased more than native and moderately oxidized 125I-LDL. LPL increased the binding of moderately oxidized 125I-LDL to the ECM more than native 125I-LDL, while it had only a small effect on strongly oxidized 125I-LDL. LPL-mediated binding of native and oxidized 125I-LDL decreased with the development of atherosclerotic lesions. Calcium ions also increased the binding of LDL to the ECM. This enhanced binding increased with the extent of LDL oxidation, especially at the early stage of atherogenesis, and decreased with lesion progression. These data suggest that the ability of ECM to retain LDL in arterial intima depends on LDL oxidation status and changes with the progression of atherogenesis. In addition, LPL and calcium ions may participate in the retention of LDL in vivo.