The perineurium of peripheral nerves is a cellular sleeve which surrounds and isolates the endoneurium with its axons and Schwann cells from the epineurium. Basement membrane covers the inner and outer surfaces of perineurial cells. This study concerns ultrastructural thickness measurements of human sural nerve perineurial cell basement membranes. Twenty-four patients with diabetes mellitus had a mean and standard deviation thickness of 174.1+/-76.2 nm., which was significantly greater than that found in 19 nondiabetics (67.1+/-12.8 nm., pooled variance two-tailed t-test, p less than 0.001). For 13 of the diabetics on insulin, the values were 208.4+/-78.1 nm. compared to those not on insulin (133.5+/-51.8 nm., p= 0.01). The p values when comparing male versus female sex and source of tissue from autopsy versus biopsy indicated no significant differences. This report documents that in diabetes mellitus, in addition to the well known basement membrane thickening of the microvasculature, there is also thickening of the basement membrane covering a nonvascular cell of nerve, the perineurial cell, and this this thickening is exaggerated in diabetics treated with insulin. We suggest that perineurial cell basement membrane thickness quantitation may be useful in distinguishing diabetic from nondiabetic distal symmetrial neuropathy.