Oxidative modification of lipoproteins may play a crucial role in the pathogenesis of atherosclerosis. This study was designed to examine whether increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins occur in patients with coronary artery disease. The levels of lipid peroxides, estimated as thiobarbituric acid-reactive substances (TBARS), were significantly greater in the plasma and very low density lipoprotein (VLDL) of symptomatic patients with coronary artery disease than in those of healthy persons, but the TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) showed insignificant difference between patients and normals. To evaluate the oxidative susceptibility of lipoproteins, we employed in vitro Cu2+ oxidation of lipoproteins monitored by changes in fluorescence, TBARS level, trinitrobenzene sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel electrophoretic mobility. While pooled VLDL and LDL of normal controls were oxidized at 5-10 microM Cu2+, pooled VLDL and LDL of patients with coronary artery disease were oxidized at 1-2.5 microM Cu2+, i.e., at relatively lower oxidative stress. At 5 microM Cu2+, VLDL and LDL of patients with coronary artery disease still showed a faster oxidation rate, judged by the rate of fluorescence increase, higher TBARS level, less TNBS reactivity, greater change in apo B immunoreactivity and higher electrophoretic mobility than those of normal controls. However, the difference on the oxidizability of HDL was insignificant for patients vs. normals. In conclusion, we have shown that plasma VLDL and LDL of patients with coronary artery disease are more susceptible to in vitro oxidative modification than those of healthy persons. The data suggest that enhanced oxidizability of plasma lipoproteins may be an important factor influencing the development of coronary artery disease.