4-Hydroxy-2-nonenal (HNE) an aldehydic peroxidation produce of n-6 fatty acids, is formed predominantly in model systems when redox active transition metal ions, particularly iron, are present. During cardiopulmonary bypass surgery blood is circulated and oxygenated extracorporeally, and periods of tissue ischaemia-reoxygenation are introduced. Both events cause oxidative stress with the generation of reactive forms of oxygen leading to lipid peroxidation. During bypass iron is released often saturating plasma transferrin, and resulting in the appearance of chelatable iron in the plasma. Because such forms of iron can promote HNE formation in vitro, we have studied 12 bypass patients, 5 of whom had plasma iron-overload. Our results show a greater percentage increase in HNE formation during bypass when the plasma transferrin is iron-overloaded compared with matched controls not showing iron-overload.