In order to examine the qualitative effect of different fats and specific fatty acids on plasma lipids and lipoprotein metabolism, six low fat, cholesterol-free diets were fed to young male hamsters (10/group) for a 4-week period. Fat blends were formulated with coconut oil, palm oil, soybean oil, high oleic acid safflower oil, butter, corn oil, and canola oil. Diets contained 13% energy as fat and dietary polyunsaturate/saturate ratios ranged from 0.12 to 1.04, one of which incorporated the American Heart Association-recommended concentrations of saturates, monoenes, and polyenes and another reflected the current American Fat Blend. In three diets the polyunsaturate/monounsaturate/saturate ratio was held constant while only the 12:0, 14:0, and 16:0 were varied. Plasma lipoproteins and apoproteins were assessed in conjunction with the abundance of specific hepatic and intestinal mRNA for the low density lipoproteins (LDL) receptor and various apolipoproteins associated with cholesterol metabolism. The plasma cholesterol response was lowest with the American Heart Association blend and equally elevated by the more saturated, low polyene diets (polyunsaturate/saturate, 0.12-0.38). Replacing 12:0 plus 14:0 from coconut oil with 16:0 as palm oil induced a significant increase in high density lipoprotein (HDL) cholesterol with a trend toward decreased LDL. These shifts in lipoprotein cholesterol were corroborated by measures of the LDL/HDL ratio, the plasma apolipoprotein B/apolipoprotein A1 ratio, and differences in the synthesis of apolipoproteins and the LDL receptor based on estimates of the mRNA for these proteins in the liver and gut, using specific cDNA probes for apolipoprotein A1, apolipoprotein B, apolipoprotein E, and the LDL receptor. Although it has been suggested that dietary polyenes lower total plasma cholesterol, including HDL, and that saturated fat increases both these pools of cholesterol, the current data represents the first evidence that a specific saturated fatty acid, i.e., palmitic acid, may enhance HDL production.