We investigated the in vitro effect of glycation on LDL oxidation. Native LDL (nLDL) was glycated in 0, 5, 10, or 20 mM glucose. This glycated LDL (gLDL) was oxidized by 1 microM copper ion. Compared to nLDL and gLDL, oxidized gLDL (ogLDL) has a greater negative charge. The thiobarbituric acid reactive substance (TBARS) value of ogLDL increased with the glucose concentration tested during glycation in a dose-dependent manner. OgLDL glycated in 20 mM glucose had a significantly higher TBARS level than did oxidized LDL incubated without glucose. In conclusion, LDL glycated in vitro is prone to oxidation. Thus, glycated LDL, which increases in the diabetic state, may contribute to the pathogenesis of atherosclerosis in diabetic patients.