In mice, hepatic functions can be greatly affected by dietary trans-10, cis-12-conjugated linoleic acid (CLA). However, this phenomenon has been less documented in hamsters. In the present study, male hamsters were fed two doses of the trans-10, cis-12-CLA (0.5 and 1%, w/w diet) or linoleic acid (0.5%) for 6 weeks. The effects on the liver were examined by measuring the expression of thirty-six genes representing key metabolic pathways. CLA-responsive genes and their relationships with physiological outcomes were examined by a multivariate analysis procedure. Compared with control hamsters, those receiving either 0.5 or 1% CLA exhibited similar fat loss (15-24%; P < or = 0.05) and liver enlargement (21-28%; P < or = 0.05), with no signs of steatosis. We also observed a dose-dependent increase in the transcription of genes involved in lipid breakdown and lipid harvesting from blood, and in genes related to the oxidative stress and inflammatory responses. These responsive genes varied in parallel with cell membrane lipids (R2 0.31-0.42) and to a lesser extent with liver enlargement (R2 0.22) (all P < 0.05). We conclude that in hamsters, liver enlargement induced by trans-10, cis-12-CLA is accompanied by an increased metabolic potential to process fatty acids from mobilised adipose stores. This elevated metabolic activity, comprised of anabolic pathways and their catabolic counterparts, can trigger inflammation and the oxidant stress defence pathways in a dose-dependent manner. These results provide novel insights into the mechanisms by which trans-10, cis-12-CLA affects pathways related to liver function.