There is increasing evidence that autoantibodies (AAbs) against oxidatively modified low-density lipoprotein (LDL) are present in humans and may be detected in fasting plasma. Using a standardized immunoassay for the detection of circulating levels of AAbs against malondialdehyde (MDA)-modified LDL, we examined the acute changes in AAb levels during postprandial lipemia in a group of men and women without (n = 28) and with (n = 17) normal endothelium. The presence of atherosclerotic vessel is documented by clinical evidence of coronary artery disease (CAD). In response to the oxidative stress associated with postprandial lipemia, statistically significant reductions in AAb levels were demonstrated at 2 and 4 hours postprandially by paired t test. In patients with atherosclerotic arterial wall, the mean AAb level was reduced to 90.8% of fasting levels (P < .001) after 2 hours and to 90% after 4 hours (P < .01). This acute reduction in AAbs against MDA-LDL appears to be unique to atherosclerotic patients and could not be demonstrated in young controls with healthy blood vessels. In nonatherosclerotic controls, the mean normalized levels during postprandial lipemia were not statistically different from baseline (104.5% at 2 hours and 104.6% at 4 hours). The transient reduction in AAb levels with postprandial lipemia in atherosclerotic patients could be reproduced in a subset of the CAD patients after significant improvement in the lipid profile with weight loss. In patients with atherosclerotic disease, the transient reduction in the level of circulating AAbs reflects either an increased propensity to generate oxidatively modified epitopes or a reduced capacity to remove excess modified epitopes. These data are the first in vivo demonstration of an acute change in the oxidative process during postprandial lipemia.