In a double-blind crossover study, 17 normocholesterolemic male volunteers were fed carefully designed whole-food diets in which 5% of energy was exchanged between palmitic (16:0) and lauric + myristic acids (12:0 + 14:0) whereas all other fatty acids were held constant. Resident males received each diet during separate 4-wk periods. The test diets supplied approximately 30% of energy as fat and 200 mg cholesterol/d. Compared with the 12:0 + 14:0-rich diet, the 16:0-rich diet produced a 9% lower serum cholesterol concentration, reflected primarily by a lower (11%) low-density-lipoprotein-cholesterol concentration and, to a lesser extent, high-density-lipoprotein cholesterol. No diet-induced changes were noted in the cholesterol content of other lipoproteins, nor did exchange of saturated fatty acids affect the triglyceride concentration in serum or lipoprotein fractions. These data indicate that a dietary 12:0 + 14:0 combination produces a higher serum cholesterol concentration than does 16:0 in healthy normocholesterolemic young men fed a low-cholesterol diet.