Oxidation of low density lipoproteins (LDL) appears to occur predominantly in arterial intima in microdomains sequestered from antioxidants of plasma. Therefore phenolic compounds which are able to bind LDL are good drug candidates for the effective prevention of lipid peroxidation and atherosclerotic processes. Plasma from healthy volunteers on nonsupplemented diets was incubated with virgin olive oil phenolic extracts (0-200 mg/l, caffeic acid equivalents). Phenolic compounds in LDL were measured by high-performance liquid chromatography-diode array detection (HPLC-DAD). Copper-mediated LDL oxidation was performed, and conjugated dienes formation was monitored. After plasma preincubation with olive oil phenolic compounds (OOPC), an increased OOPC-concentration dependent was observed in the total phenolic content of LDL (p < 0.001, ANOVA) as well as in the lag time before conjugated diene formation (p < 0.001, ANOVA). Rutin and four phenolics with flavonoid-like spectra were found to be bound to the LDL control. These phenolics, together with tyrosol which was not present in the LDL control, significantly increased in LDL (p < 0.05) after plasma incubation with OOPC. These results show the ability of tyrosol to bind LDL in vitro and the capacity of virgin olive oil phenolics to protect other phenolic compounds previously bound to LDL. These results provide further evidence that phenolic compounds bound to LDL are likely to protect LDL from oxidation.