Human atherosclerotic plaques contain considerable amounts of oil red O-positive material even after treatment with alcohol and xylene and embedding in paraffin wax. Much is extracellular in the advanced plaques, but very early lesions contain mononuclear cells laden with fine granules of such material. Occasionally, near advanced plaques, similar cells have also been seen in the adventitia and in nearby lymph nodes. The chemical nature of the insoluble lipids has not been investigated, but it is suggested that they represent oxidized lipids which are potentially toxic and might play an important part in the establishment of the plaque.