To determine the effects of three saturated fatty acid combinations on lipoprotein metabolism, we fed 18 21- to 32-year-old men three diets in a crossover design for 28-day periods separated by washout periods of 4 to 6 weeks. The men self-selected a prescribed diet at home emphasizing saturated fat as the visible fat for 1 week. Then, they ate experimental diets providing 40%, 15%, 17%, and 7% of food energy, respectively, as total, saturated, monounsaturated, and polyunsaturated fatty acids, levels representing amounts available in the US diet. Different test fatty acid combinations, given at 4 to 6 energy% (en%) each, were incorporated into food products: 12:0 + 14:0, 14:0 + 16:0, and 16:0 + 18:0. Test fatty acids were equalized by giving free myristic acid (14:0) with palm kernel oil or butter and sheanut butter (high in 18:0) with lard. The diet highest in 12:0 + 14:0 also provided 4.2 en% 16:0, the most common saturated fatty acid in the US diet. Mean apparent absorption of all fatty acids was at least 90%. The three diets produced similar concentrations of serum total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B-100 regardless of the apo E phenotype of the subjects. Compared with baseline, the experimental diets affected serum high-density lipoprotein (HDL) concentrations (P < .06), with the highest values occurring on diet 12:0 + 14:0. When the change from baseline in receptor-mediated degradation of 125I-LDL in freshly isolated mononuclear cells (MNC) was stratified by apo E phenotype, diet 16:0 + 18:0 produced a 30% increase, compared with a 9% decrease on diet 12:0 + 14:0 and a 6% increase on diet 14:0 + 16:0 in subjects with the apo E3/3 phenotype. These results suggested that different saturated fatty acid combinations, consumed at levels typical of availability in the United States and with diets providing ample unsaturated fat, had similar cholesterolemic properties in healthy males despite some subtly different effects on lipoprotein metabolism.