Our purpose was to elucidate the mechanisms whereby diets high in polyunsaturated fat lower plasma triglycerides and HDL cholesterol concentrations compared with diets high in saturated fat. Twenty-four male Golden Syrian hamsters (F1B strain) were fed semipurified diets containing 0.2 g cholesterol + 15 g fat/100 g diet enriched (13 g/100 g) in either coconut oil or soybean oil for 18 wk. Consumption of the soybean oil diet was associated with significantly (P < 0.001) lower mean concentrations of HDL cholesterol (28%), triglycerides (51%) and free fatty acids (51%), as well as a significantly lower proportion of large HDL particles. No effect on plasma cholesteryl ester transfer protein or lecithin:cholesterol acyltransferase activities or hepatic or intestinal apolipoprotein (apo) A-I, A-IV or E mRNA levels were noted. The soybean oil-fed group had significantly lower levels of mRNA (P < 0.05) for hepatic apo A-II (23%) and apo C-III (18%) and significantly higher levels of mRNA for intestinal apo C-II (23%). Our data are consistent with the hypothesis that diets high in polyunsaturated fatty acids lower triglyceride concentrations in hamsters by decreasing apo C-III gene expression and by increasing apo C-II gene expression. In addition, reduced expression of apo A-II in animals fed the soybean oil diet may contribute to the lower HDL cholesterol concentration and larger proportion of small HDL particles noted.