Oxidatively-modified low-density lipoproteins (LDL) contribute to the onset of the atherosclerotic disease. A recently discovered marker of lipid peroxidation in a series of prostaglandin F2-like compounds, the prostaglandin isomers isoprostanes, that are generated from arachidonic acid through cyclooxygenase-independent pathways following free radical injury and are endowed with potent biological activities. The incidence of cardiovascular disease in the Mediterranean area is low, possibly because of the type of fat (mainly olive oil) and other components (e.g. fruits and vegetables) of the diet. Natural antioxidants abound in this kind of diet and may also contribute to the observed protection from coronary heart disease (CHD) by retarding the formation of the atherosclerotic plaque. Olive oil, the major dietary fat in the Mediterranean countries, is rich in phenols with antioxidant properties. We thus investigated the formation of isoprostanes during in vitro LDL oxidation and tested the effect of an olive-oil-extracted phenol (i.e. hydroxytyrosol). Our data show that production of isoprostanes and other markers of lipid peroxidation occurs during LDL oxidation and is inhibited by hydroxytyrosol.