Foods contain isomers of unsaturated fatty acids that have double bonds in unusual configurations (trans instead of cis) or unusual positions, or both. Such fatty acids arise through biohydrogenation in the rumen of cows and sheep or catalytic hydrogenation in industrial hardening of oils. The effects of transmonounsaturates on lipoproteins in man are opposite to those of their cis-isomer, oleic acid: trans fatty acids raise low density lipoprotein (LDL) cholesterol and lipoprotein Lp(a) and lower high density lipoprotein (HDL) cholesterol, all in a dose-dependent fashion. Trans fatty acids raised serum cholesteryl ester transfer activity in 52 of 55 volunteers (mean change 18%, P < 0.02), and lowered the ratio of cholesteryl esters to triglycerides in HDL. Lecithin cholesterol acyl transferase was unchanged. The effects of trans fatty acids on HDL and LDL may thus be mediated through cholesterol ester transfer protein.