Human monocyte-macrophages were incubated for 24 h with low-density lipoprotein (LDL) which had been previously oxidized for varying periods up to 24 h with copper ions, in the presence or absence of DL-alpha-tocopherol or probucol. The release of radioactivity from cells preloaded with tritiated adenine was used as an assay of toxicity. Toxicity of oxidized LDL increased with duration of copper oxidation and with increasing evidence of lipid oxidation, measured by assay of thiobarbituric acid-reactive substances and by gas chromatography. Oxidation and toxicity were inhibited by DL-alpha-tocopherol (200 microM) and probucol (50 microM).