The murine monoclonal antibody mAb-1H11 raised against malondialdehyde (MDA)-modified LDL, was used to detect cross-reacting material in human atheromatous tissue and in plasma. MDA-modified LDL levels in plasma were 0.19 +/- 0.02 mg/dl (mean +/- SEM) in 44 control subjects, 0.24 +/- 0.02 mg/dl in 15 patients with chronic stable angina pectoris (P = NS vs LDL cholesterol matched controls), 1.4 +/- 0.1 mg/dl in 60 patients with acute myocardial infarction (P < 0.001 vs controls), and 0.86 +/- 0.11 mg/dl in 22 patients with carotid atherosclerosis (P < 0.001 vs controls). Modified LDL, isolated from pooled LDL of 10 patients, showed a higher electrophoretic mobility on agarose gels, a higher content of thiobarbituric acid reactive substances, and a higher cholesterol/protein ratio than native LDL and had a similar reactivity (antigen/protein ratio) in the assay as the in vitro MDA-modified LDL used for calibration. Its apo B-100 moiety was not fragmented. Uptake of this modified LDL by macrophages resulted in foam cell generation. In conclusion, elevated plasma levels of atherogenic MDA-modified LDL may be a marker for unstable atherosclerotic cardiovascular disease.