BACKGROUND Fatty acids that contain a trans double bond are consumed in large amounts as hydrogenated oils, but their effects on serum lipoprotein levels are unknown. METHODS We placed 34 women (mean age, 26 years) and 25 men (mean age, 25 years) on three mixed natural diets of identical nutrient composition, except that 10 percent of the daily energy intake was provided as oleic acid (which contains one cis double bond), trans isomers of oleic acid, or saturated fatty acids. The three diets were consumed for three weeks each, in random order. RESULTS On the oleic acid diet, the mean (+/- SD) serum values for the entire group for total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were 4.46 +/- 0.66. 2.67 +/- 0.54, and 1.42 +/- 0.32 mmol per liter (172 +/- 26, 103 +/- 21, and 55 +/- 12 mg per deciliter), respectively. On the trans-fatty-acid diet, the subjects' mean HDL cholesterol level was 0.17 mmol per liter (7 mg per deciliter) lower than the mean value on the diet high in oleic acid (P less than 0.0001; 95 percent confidence interval, 0.13 to 0.20 mmol per liter). The HDL cholesterol level on the saturated-fat diet was the same as on the oleic acid diet. The LDL cholesterol level was 0.37 mmol per liter (14 mg per deciliter) higher on the trans-fatty-acid diet than on the oleic acid diet (P less than 0.0001; 95 percent confidence interval, 0.28 to 0.45 mmol per liter) and 0.47 mmol per liter (18 mg per deciliter) higher on the saturated-fat diet (P less than 0.001; 95 percent confidence interval, 0.39 to 0.55 mmol per liter) than on the oleic acid diet. The effects on lipoprotein levels did not differ between women and men. CONCLUSIONS The effect of trans fatty acids on the serum lipoprotein profile is at least as unfavorable as that of the cholesterol-raising saturated fatty acids, because they not only raise LDL cholesterol levels but also lower HDL cholesterol levels.