It is commonly believed that low-density lipoproteins (LDLs) carry cholesterol into the artery wall. In addition, some epidemiologic studies have suggested that triglyceride-rich lipoproteins, such as very-low-density lipoproteins (VLDLs), may be much less important than LDLs in atherogenesis. To determine if VLDLs or their metabolic remnants could have a direct role in the formation of atherosclerotic plaque, we examined lipoproteins isolated from endarterectomy specimens. Atherosclerotic plaque was obtained from eight subjects who underwent aortoiliac endarterectomy (4), aortic aneurysm repair (2), or visceral/renal endarterectomy (2). Plaques were washed extensively, minced, and incubated with a buffered saline solution. Lipoproteins were recovered from this solution via a selected-immunoaffinity column by means of a polyclonal antibody to human LDL (apolipoprotein B-100). Particle sizing from electron photomicrographs of negatively stained specimens indicated that 8% of the lipoprotein particles were the size of plasma VLDL (350 to 800 nm). Thirty-six percent were the size of plasma VLDL remnant particles (250 to 350 nm), and 56% were consistent in size with plasma LDL (175 to 250 nm). We conclude that VLDL- and VLDL remnant-sized particles appear to comprise a significant percentage of the lipoproteins found in human atherosclerotic plaque and could have a direct role in the atherosclerotic process.