The role of inflammation in atherosclerotic disease is well established, but the role of autoantibodies against modified apolipoprotein (apo) B-100 remains unclear. The metabolic syndrome is associated with a proinflammatory state, a predominance of small dense low-density lipoprotein (LDL) particles, and an increased risk for atherosclerotic diseases. Previous studies have shown specific autoantibodies against modified apo B-100 (within LDL) to be related to human atherosclerotic disease. The objective of the present study was to investigate whether autoantibodies against modified apo B-100 are related to parameters of the metabolic syndrome, such as small dense LDL. Two hundred ninety-one healthy men were investigated for different metabolic, anthropometric, and inflammatory variables; LDL peak particle size; and distribution of LDL in 4 subfractions. Subjects were grouped according to LDL peak size > or = 23.5 nm (pattern A, n = 230) or <23.5 nm (pattern B, n = 61). Immunoglobulin (Ig) G and IgM antibodies against 2 aldehyde-modified peptide sequences, denoted as 45 and 210, within apo B-100 were quantified. Levels of IgG(45), but not the other autoantibodies, were significantly higher in pattern B individuals (with a predominance of small dense LDL particles) compared with pattern A (P < .01). Relationships for both IgG(45) and IgG(210) with parameters typically associated with the metabolic syndrome were found. Only IgG(45) tended to be higher in individuals with the metabolic syndrome compared with those without (P = .07). We conclude that subjects with a predominance of small dense LDL particles have elevated concentrations of IgG(45) in the circulation, which reflect an activated immune response to a specific epitope of modified apo B-100.