The involvement of low density lipoprotein (LDL) peroxidation in atherogenesis is now admitted. The oxidation of high density lipoproteins (HDL) could contribute to the atherogenic process, by limiting their capacity to accept cholesterol from cell membranes. In this work, we studied the human HDL peroxidation initiated by OH. or OH./O2.- free radicals generated by gamma radiolysis. This method allows a quantitative and selective production of free radicals, and the resulting oxidation is less drastic than the chemical one. HDL oxidation was followed, as a function of the radiation dose, by the disappearance of endogenous vitamin E, the formation of thiobarbituric acid-reactive substances (TBARS) and the fluorescence at 440 nm. Human HDL turned out to be oxidizable by hydroxyl free radicals and oxygen potentiated this effect. The oxidative modification of HDL, leading to a rigidification of the HDL envelop, could contribute to reduce the ability of HDL to stimulate efflux of cholesterol from tissues.