Small low density lipoproteins (LDL) are more susceptible to in vitro oxidation than larger LDL. To study whether this leads to more oxidation of small LDL in vivo, we determined the level of autoantibodies against malondialdehyde-modified LDL (MDA-LDL) in subjects with small or large LDL (LDL subclass pattern B or A) by ELISA. The study group consisted of 92 subjects with coronary heart disease without severe hypercholesterolemia (mean total plasma cholesterol 5.9 +/- 0.8 mM), 46 with an LDL subclass pattern A and 46 with an LDL subclass pattern B. In the subjects with LDL subclass pattern B the titre of autoantibodies of the IgM class against MDA-LDL was 29% higher than in the subjects with LDL subclass pattern A (P < 0.0001). The concentration of the anti-MDA-LDL autoantibodies of the IgM class was 58% higher in the patients with the pattern B than in the patients with the pattern A (P < 0.0001). There was no statistically significant difference in the titre or concentration of autoantibodies of the IgG class between subjects with LDL subclass patterns A and B. Besides plasma triglyceride and HDL cholesterol, the titre and concentration of the IgM autoantibodies were found to be independent predictors of the LDL subclass pattern. These results show that small LDL are associated with higher autoantibody levels than large LDL. Based on the assumption that the level of autoantibodies against MDA-LDL represents the rate of LDL oxidation in vivo, we conclude that in vivo small LDL is more readily oxidised than larger LDL.(ABSTRACT TRUNCATED AT 250 WORDS)