Nonenzymatic glycation of neural proteins could underlie diabetic peripheral neuropathy. Cytoskeletal and myelin protein fractions of central nervous system and peripheral nervous system (PNS) tissue from rats with streptozotocin-induced diabetes of 1.5 and 8 months duration were analyzed for glycation products. In sciatic nerve cytoskeletal preparations from both diabetic and control animals we found high levels of the early glycation product (measured as furosine) after 6 weeks, which had fallen markedly by 8 months. Conversely the advanced glycation end product (AGE), pentosidine, was low at 6 weeks and high by 8 months in diabetic animals. The levels of glycation products were much lower in spinal cord and spinal nerve from diabetic animals. There was increased borotritride labeling of neurofilament subunits, and of cross-linked material, in cytoskeletal fractions of diabetic sciatic nerves. These results show that the PNS cytoskeleton is vulnerable to nonenzymatic glycation, resulting in AGE formation, in diabetic rats and to a lesser extent in normals.