The effects of dietary fat saturation on the metabolism of low-density Iipoprotein (LDL) subtractions were measured in adult male guinea pigs fed semipurified diets containing 15% (wt/wt) corn oil (CO; 58% llnoleic acid), lard (24% palmitic/14% stearic acid), or palm kernel oil (PK; 52% lauric/18% myristic acid). Animals fed the CO diet had lower plasma total cholesterol levels than guinea pigs fed the PK or lard diets (p<.01). Plasma LDL-1 (<f=1.019 to 1.05 g/mL) concentrations were 3.5- and 2.4-fold higher in animals fed the PK diet compared with the CO and lard groups, respectively, while LDL-2 (d=l.OS to 1.09 g/mL) concentrations were not different among groups. For all dietary fat groups LDL-1 had a higher molecular weight and a larger diameter than LDL-2. LDL fractional catabolic rates (FCRs) varied, depending on both the diet and the LDL subtraction. Animals fed the poiyunsaturated CO diet had a more rapid LDL FCR than animals from the other two groups (7><.01). Within the same diet group, LDL-2 exhibited a slower turnover rate than LDL-1 in animals fed the PK diet, while no differences in LDL subtraction FCR were found in the CO and lard groups. Animals fed the PK and lard diets did not exhibit significant modifications in the density distribution of LDL subtractions over a period of 33 hours. In contrast, animals fed the CO diet exhibited a shift of more buoyant to denser LDL particles, suggesting that differences in LDL intravascular processing are mediated by dietary fat saturation. In vitro LDL binding to hepatic membranes confirmed the in vivo data with an increased expression of apolipoprotein B/E receptors (Bm) in animals fed the CO diet (p<.01). Hepatic apolipoprotein B/E receptors exhibited less affinity for LDL-2 in the PK group, a result consistent with the less rapid turnover of LDL-2 in PK-fed animals. The results suggest that dietary fatty acids varying in saturation and composition have distinctive atherogenic potentials. The lowest plasma LDL cholesterol concentrations mediated by CO intake could in part be explained by induced changes in the composition and processing of LDL subtractions, resulting in faster LDL turnover rates in addition to increased expression of hepatic apolipoprotein B/E receptors. Similarly, the hypercholesterolemic effects of the lard and PK diets appear to be related to differences in intravascular processing of LDL subtractions, with no interconversion between LDL-1 and LDL-2 and that is accompanied by decreased expression of hepatic apo B/E receptors. In addition, PK-fed guinea pigs exhibited a decreased apolipoprotein B/E receptor affinity for LDL-2. {ArterioscUr Thromb. 1993;13:1418-1428.