The lumbosacral spinal cord, lumbar roots, L5 spinal ganglion, L5 segmental nerve and entire lengths of the sciatic, tibial, peroneal and sural nerves were taken at postmortem examination from 2 patients with insulin-dependent diabetes mellitus (IDDM) and a predominantly sensory symmetric distal polyneuropathy and compared with 2 non-diabetic control patients. Sections from proximal to middle levels of sciatic nerves of these patients showed a remarkable variability in myelinated fiber (MF) density within and between fascicles. Roots and segmental nerves appeared to be unaffected. Sections of peroneal, tibial and sural nerves showed only severe and diffuse fiber loss. The findings suggest that multifocal lesions at upper levels of sciatic nerve can summate distally to produce a symmetric diabetic neuropathy. The findings, if confirmed by using quantitative approaches in larger numbers of patients, suggest an underlying interstitial pathological process rather than a metabolic process.