The alpha-dicarbonyl compounds formed in vivo by oxidative or non-oxidative ways react with amino groups of proteins to form cross-linked stable end products called glycation end products (AGEs) or Maillard products, which are not well characterized. The AGEs are irreversibly formed and found to accumulate with aging, atherosclerosis, and diabetes mellitus, especially those associated with long-lived proteins, such as collagens, lens crystallines, and nerve proteins. The formation of AGEs was implicated to not only modify protein properties, but also to induce biological damage in vivo. In order to elucidate the mechanism for this damaging reaction, we previously reported the model study of the reaction between alpha-dicarbonyl methylglyoxal and amino acids. Our results showed that three types of free radical species were produced in the glycated products and their structures were identified using EPR spectroscopic methods. These free radicals are: (1) crosslinked radical cations, the methylglyoxal dialkylimine radical cations; (2) the methylglyoxal radical anions; and (3) the superoxide radical anions generated only in the presence of oxygen molecules. We suggested that the stable cross-linked radical cation or its precursor, the cross-linked dialkylimine, could be a reactive site for putative reducing and oxidizing molecules, which produce free radicals for a long duration. We obtained supporting experimental evidence from the study with glycated bovine serum albumin (JBC, in press, 1998), which demonstrate that the cross-linked Schiff base and the cross-linked Schiff base radical cation of the protein exhibits enzyme-like characteristics for the generation of free radicals. These results together indicate that long-lived glycated proteins accumulated in vivo may contribute to accelerating oxidative modification of vascular wall lipids in diabetes and atherosclerosis.