Sural nerve lesions in patients with clinically manifest diabetic neuropathy were investigated electron microscopically. Myelinated nerve fibers were reduced in all the diabetic patients. Axonal degeneration of both myelinat-ed and unmyelinated nerve fibers was most conspicuous finding in the diabetic sural nerves. Structural changes of the axons were represented by axonal dwindling, depletion of axoplasmic organelles, vacuolarization and an increase in neurofilaments. Accumulation of glycogen-like particles and deposition of electron homogeneous amorphous materials were noted within a few axons. On the other hand, there could also be found degenerative changes of myelin sheaths, various kinds of cytoplasmic inclusion bodies (crystalloid, lamellar inclusion bodies and lipids-like droplets), aggregates of glycogen particles in the Schwann cell cytoplasm and basement membrane hyperplasia of Schwann cells in all the subjects. Furthermore, multiplication and thickening of the basement membrane of vasa nervorum were constant findings of the diabetic sural nerves. The vascular changes, demyelination and axonal degeneration of the cases were not apparently correlated with each other. There was no special relationship between nerve tissue changes and clinical symptoms or laboratory findings. These results indicated that the peripheral nerve lesions in human diabetics were mainly due to metabolic impairment of nerve fibers, accompanying dysmetabolism of Schwann cells and diabetic microangiopathy, and that these changes proceeded independently