An antioxidant defense system consisting of enzymes and non-enzymatic compounds prevents oxidative damage of lipoproteins in the plasma. When the activity of this system decreases or the reactive oxygen species (ROS) production increases, an oxidative stress may occur. Since fatty acids and triglyceride-rich emulsions can stimulate leukocytes to produce ROS, it is conceivable that raised plasma triglyceride-rich lipoproteins such as very low density lipoprotein (VLDL) may overload the antioxidant system. To test this hypothesis, we selected 14 patients with combined hyperlipidemia (HLP), in whom low density lipoprotein (LDL) and VLDL levels are elevated, as well as 18 hypercholesterolemic patients (HCH) with increased LDL levels and 19 controls (NL) to examine the trend for an imbalance between the production of oxidative species and the antioxidant defense system as challenged by increased plasma lipids. With this goal, plasma lipoprotein lipid fractions were determined and correlated with the release of ROS by leukocytes monitored by luminol-enhanced chemiluminescence. Plasma beta-carotene, alpha-tocopherol, lycopene and the lipoprotein lipid hydroperoxides were determined by high pressure liquid chromatography with electrochemical detection. HLP had lower plasma superoxide dismutase (SOD) activity (0.04 and 0.11 U/mg protein; P < 0.05) as well as lower concentrations of lycopene (0.1 and 0.2 nmol/mg cholesterol; P < 0.05) and beta-carotene (0.8 and 2.7 nmol/mg cholesterol; P < 0.05) in the plasma, as compared with NL. Moreover, HLP showed the highest ROS production by resting mononuclear leukocytes (MN) among the three study groups. When the results of the subjects of the three groups were taken together, the plasma triglyceride concentration was positively correlated to ROS release by resting polymorphonuclear leukocytes (PMN, r = 0.38, P = 0.04) and MN (r = 0.56, P < 0.005). Moreover, ROS release by resting MN was positively correlated with VLDL (r = 0.47, P = 0.02) and LDL (r = 0.57, P = 0.01) triglycerides. There was also a positive correlation between ROS release by stimulated PMN and VLDL (r = 0.44, P = 0.03) as well as LDL (r = 0.53, P = 0.01) triglycerides. High density lipoprotein (HDL) cholesterol showed a negative correlation with ROS release by resting MN (r = -0.48, P = 0.02) and resting PMN (r = -0.49, P = 0.01). VLDL susceptibility to copper (II) oxidation was not different among the three groups. Regarding LDL, there was an increased oxidizability in HLP group.(ABSTRACT TRUNCATED AT 400 WORDS)