The trans isomer of oleic acid (elaidic acid) increases low density lipoprotein (LDL) cholesterol and decreases high density lipoprotein (HDL) cholesterol in man. One possible mechanism for this effect is that trans fatty acids increase plasma cholesteryl ester transfer protein (CETP) activity. We examined the effect of dietary trans fatty acids on activity of this protein in plasma from 27 men in a double blind crossover comparison. The background diet, containing 15% energy as fat from dairy products, meat, bread and cereals, was supplemented with oleic or elaidic acid providing a further 20% energy. The elaidic supplement provided about 6% energy as trans fatty acid. Activity of CETP in plasma was significantly higher (P < 0.001) after the elaidic acid-rich diet (23.95 +/- 1.26%) compared with the diet enriched with oleic acid (19.61 +/- 0.89%). A significant correlation between the change in plasma trans 18:1 fatty acids and the change in plasma CETP activity (r = 0.58, P < 0.002) was independent of changes in LDL-cholesterol. The increase in CETP activity was in turn significantly correlated with a fall in HDL-cholesterol among subjects during the elaidic acid-rich period (r = -0.57, P < 0.01). We have shown that CETP demonstrates substrate specificity and that the increase in activity with dietary trans fatty acids may contribute to a more atherogenic lipoprotein profile.