Differences in dietary fatty acid structure induce marked differences in lipid and lipoprotein concentrations in plasma from fasting subjects. Under metabolic-ward conditions, replacement of carbohydrates by lauric, myristic, and palmitic acids raise both low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol whereas stearic acid has little effect. Oleic and linoleic acids raise HDL and slightly lower LDL; all fatty acids lower fasting triglycerides when substituted for carbohydrates. Trans monounsaturates lower HDL and raise LDL and lipoprotein(a). The fatty acids in unhydrogenated fish oil potently lower triglycerides, with variable effects on LDL. Of the commercial fats, palm-kernel and coconut oil are the most hypercholesterolemic, followed by butter and palm oil. Replacement of hard fats rich in lauric, myristic, or palmitic acids or trans fatty acids by unsaturated oils will lower LDL, but replacement by carbohydrates will in addition decrease HDL and increase triglycerides. In free-living subjects, high-oil diets could lead to obesity, undoing the favorable effects on HDL and triglycerides.