We found that allopurinol, at therapeutically relevant concentrations (9-58 microM), significantly counteracted copper-catalysed human non-HDL lipoprotein oxidation, as assessed by thiobarbituric acid reactant content and kinetics of conjugated diene formation. Oxypurinol was ineffectual. Both drugs had no activity on metal-independent, peroxyl radical-induced lipoprotein oxidation. Specific fluorescence-quenching experiments revealed that only allopurinol could interact with copper antagonizing metal binding to lipoproteins. Thus, therapeutic allopurinol concentrations can inhibit copper-catalysed lipoprotein oxidation through metal complexation, suggesting some antioxidant-antiatherogenic activity of the drug in vivo.