The microvessels in the buttock skin of 15 patients with long-standing juvenile diabetes were studied both by electron microscopy and three-dimensional (3D) computer reconstruction of a prototypical diabetic postcapillary venule. Endothelial cell gaps were found in postcapillary venules and capillaries, but only in association with an increased deposition of basement membrane-like material in the vascular wall. In parallel with the increased amounts of deposited basement membrane-like material, the space between pericytes and endothelial cells was wider and the cytoplasmic processes that formed the contact points between them were longer and thinner than normal. Pericytes, devoid of any cytoplasmic contacts with the underlying endothelial cells, were observed as isolated cells within the outer third of the vascular wall in markedly thickened vessels. These observations offer an explanation for the known increased vascular permeability of diabetic vessels, and suggest a possible explanation for the development of diabetic retinopathy with aneurysm formation.