In human diabetes mellitus, thickening of the microvascular endothelial cell basement membrane has been documented by quantitative ultrastructural studies in a variety of vascular beds. We studied the thickness of the cerebral cortical capillary basement membrane in frontal and occipital lobes from 21 diabetics and 16 nondiabetics, and found that those from diabetics were significantly thicker. Skeletal muscle capillary basement membranes have been shown to thicken with increasing age. However, only in the frontal cortex of diabetics was a significant relationship observed between capillary basement membrane thickening and increasing age. We conclude that, along with many of the previously studied microvascular beds, the cerebral cortical microvasculature displays thickening of the endothelial cell basement membrane in diabetes mellitus. No currently known disease is associated with this microvascular change, unlike the closely related retinal vasculature, where the association with diabetic retinopathy is established.