Human studies suggest that CLA changes metabolism, possibly through effects on mRNA expression of desaturase and elongase enzymes. In this respect, differential effects of the two most common dietary CLA isomers, cis-9,trans-11 (c9,t11) and trans-10,cis-12 (t10,c12) CLA, have hardly been studied. We therefore gave 25 healthy, overweight men and women daily for 6 wk a drinkable dairy product containing 3 g of oil that was rich in oleic acid. For the next 18 wk, the control group (n = 7) continued to use this product, whereas the second (n = 9) and third groups (n = 9) received products with 3 g of purified c9,t11 CLA or t10,c12 CLA. For each gram of c9,t11 CLA consumed, the proportion in plasma phospholipids increased by 0.26%. For t10, c12 CLA, this value was 0.20%. The t10,c12 CLA isomer increased plasma TAG levels of conjugated 18:3, whereas c9,t11 CLA increased those of both conjugated 18:3 and 20:3. In plasma phospholipids, the delta9 desaturation index of 18:0 (18:1 n-9/18:0) was decreased by t10,c12 CLA (P= 0.03 for diet effects), and the delta6 desaturation index [(18:3n-6 + 20:3n-6)/18:2n-6] was decreased by both CLA isomers (P < 0.01 for diet effects). The delta5 desaturation index (20:4n-6/20:3n-6) and the delta9 desaturation index of 16:0 (16:1 n-7/16:0) were not affected. No effects were seen on mRNA expression of desaturases and elongase in peripheral blood mononuclear cells (PBMC). We therefore conclude that incorporation of c9,t11 and t10,c12 CLA into plasma lipids reflects dietary intakes. Compared with oleic acid, delta9 and delta6 desaturation indices in plasma phospholipids are decreased after consumption of c9,t11 or t10,c12 CLA. Effects on desaturation indices were, however, not reflected by changes at the transcriptional level for the various desaturases and elongase enzymes in PBMC.