Apolipoprotein E isomorphs in very low density lipoproteins and apolipoprotein B of low density lipoproteins were measured in the plasma of normolipidemic subjects with xanthelasmas of the eyelids and in appropriate control groups. All patients tested in the experimental group had an apolipoprotein EII to apolipoprotein EIII ratio typical of the heterozygous state for familial dysbetalipoproteinemia, a hyperapobetalipoproteinemia, or both. Some patients had concomitant atherosclerosis. This is the first report of an increased frequency of the apolipoprotein E-ND phenotype in normolipidemic xanthelasma. This condition should not be dismissed as benign; tissue lipid deposition in the absence of hyperlipidemia might be related to the presence of lipoproteins of abnormal composition with an enhanced atherogenic potential.