Advanced nonenzymatic glycosylation products capable of cross-linking proteins accumulate on collagen in vivo in proportion to time-averaged blood glucose concentration. In this report, we have evaluated the ability of advanced nonenzymatic glycosylation products formed on collagen in vitro to covalently bind low-density lipoprotein (LDL) in a manner similar to that which occurs in human atherosclerotic lesions. At constant LDL concentration, covalent trapping increased linearly with the extent of advanced glycosylation product formation, from 1.42 +/- 0.15 to 4.46 +/- 0.36 micrograms LDL protein/mg collagen. At a constant level of collagen advanced glycosylation product, LDL binding increased as a function of increasing LDL concentration. At an LDL-cholesterol level of 103 mg/dl, covalent trapping of LDL by nonenzymatic glycosylation products on collagen averaged 3.2 times as much as control (P less than 0.01). These data indicate that LDL is bound specifically by reactive products generated by nonenzymatic glycosylation of collagen, and suggest that excessive LDL trapping by hyperglycemia-induced advanced glycosylation endproducts may contribute to the accelerated development of atherosclerosis in patients with diabetes mellitus.