The effects on plasma lipoproteins and apolipoproteins of replacing corn oil with corn-oil margarine in stick form as two thirds of the fat in the National Cholesterol Education Program (NCEP) Step 2 diet were assessed in 14 middle-aged and elderly women and men (age range, 44-78 years) with moderate hypercholesterolemia (low density lipoprotein cholesterol [LDL-C] range, 133-219 mg/dl [3.45-5.67 mmol/1] at screening). During each 32-day study phase, subjects received all their food and drink from a metabolic kitchen. Subjects were first studied while being fed a diet approximating the composition of the current US diet (baseline), which contained 35% of calories as fat (13% saturated fatty acids [SFAs], 12% monounsaturated fatty acids [MUFAs; 0.8% 18:ln-9trans], and 8% polyunsaturated fatty acids [PUFAs]) and 128 mg cholesterol/1,000 kcal. This baseline phase was followed by a corn oil-enriched diet containing 30% fat (6% SFA, 11% MUFA [0.4% 18:ln-9trans], and 10% PUFA) and 83 mg cholesterol/ 1,000 kcal, and then a corn-oil margarine-enriched diet containing 30% fat (8% SFA, 12% MUFA [4.2% 18 1n-9trans], and 8% PUFA) and 77 mg cholesterol/1,000 kcal. All diets were isocaloric Mean fasting LDL-C and apolipoprotein (apo) B levels were 153 mg/dl (3.96 mmol/1) and 101 mg/dl on the baseline diet, 17% and 20% lower (bothp<0.001) on the corn oil-enriched diet, and 10% and 10% lower (bothp<0.01) on the margarine-enriched diet Mean fasting high density lipoprotein cholesterol (HDL-C) and apoA-I levels were 48 mg/dl (1.24 mmol/1) and 134 mg/dl on the baseline diet, 9% and 0.4% lower on the corn oil-enriched diet (p<0.01 for HDL-C), and 10% and 3% lower on the margarine-enriched diet (p<0.01 for HDL-C). No significant effects of diet on trigryceride, apoA-I, or lipoprotein(a) concentrations were noted. Replacing corn oil with a typical corn-oil margarine in stick form, as is currently available, resulted in a 10-fold increase in dietarytransfatty acid intake as well as 21% and 14% increases in SFA and MUFA intake, respectively, and a 12% decrease in PUFA intake. These changes resulted in higher plasma concentrations of total cholesterol (p=0.039), LDL-C (p=0.058), and LDL apoB (p=0.068) and a less favorable total cholesterol to HDL-C ratio (p=0.037). Both experimental diets resulted in significant reductions in plasma cholesterol relative to the baseline diet; however, the differences resulting from the substitution of the corn-oil margarine for corn oil were associated with a less favorable lipid profile with regard to coronary heart disease risk. We therefore recommend that hydrogenation be minimized during the processing of foods for use in cholesterol-lowering diets.