For clinical and epidemiological screening a simple and sensitive methodology was developed for detection of preformed lipid peroxides (LPO) in low density lipoprotein (LDL). For this purpose, the iodometric assay of El-Saadani et al. (J Lipid Res 1989;30:627-30) was adapted to the fraction containing LDL isolated by polyanion precipitation avoiding ultracentrifugation. This fraction also includes intermediate density lipoprotein. Stratifying 53 individuals by their serum triglyceride levels (TG) the highest quartile showed a highly significant elevation of LDL-LPO compared with the lowest one (69.2 +/- 41.2 vs 22.9 +/- 10.0 nmol mg-1 LDL-apo B, P < 0.001). LDL-LPO concentration also showed a strong correlation with TG (r = 0.73, P < 0.00001) and significant inverse correlations with high density lipoprotein cholesterol (HDL-C) and HDL3-C subfraction (r = -0.37, P < 0.01 and r = -0.38, P = 0.01, respectively). The TG/HDL-C ratio, which is closely associated with insulin resistance, was strongly correlated with LDL-LPO (r = 0.83, P < 0.00001). Significant elevations of LPO were observed in phenotypic hyperlipoproteinemias (HLP) IIb and IV (P < 0.01 and P < 0.02, respectively) and when expressing LPO in mol/mol of LDL-apo B, two- and 2.5-fold higher values were found in types IIb and IV HLP, respectively, compared with normolipidemic subjects, suggesting a more oxidative environment for apo B in both phenotypes. No variations in LPO were found in type IIa HLP. This simple assay for in vivo detection of LDL-LPO, emphasises the possible atherogenic effect of TG through their oxidative capacity and suggests the integration of LPO to the cluster of associated risk factors: high TG, low HDL-C and insulin resistance.