The effects of natural mixed diets on lipid peroxidation were investigated in humans. In the first study, 59 subjects were fed a rapeseed oil-based diet rich in monounsaturated fatty acids (MUFA) and a sunflower oil-based diet rich in polyunsaturated fatty acids (PUFA) in a cross-over manner for three and a half weeks. The lipid peroxidation products in plasma were determined by measuring conjugated dienes and malondialdehyde (MDA). In a second study, plasma thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and the susceptibility of very low density lipoprotein+low-density lipoprotein (LDL) to in vitro oxidation were measured from subjects fed similar MUFA and PUFA diets for six weeks diets. No significant differences in plasma MDA or conjugated diene concentrations were found after the rapeseed oil diet or the sunflower oil diet in Study 1. In the second study, a small but significant decrease (P < 0.05) in both lipid hydroperoxides and TBARS was observed in the LDL fraction after the sunflower oil diet. The in vitro oxidation gave opposite results, showing increased oxidation after the sunflower oil diet. Despite a high intake of alpha-tocopherol during the oil periods, no increase in plasma alpha-tocopherol was noticed in either study. The results suggest that moderate changes in the fatty acid composition in the Western-type diet may be adequate to affect lipoprotein susceptibility to oxidation in vitro, but there is considerable disparity with some indices of in vivo lipid peroxidation.