Molecular size has been considered in the past to be the major factor in glomerular restriction of macromolecules. Ultrastructural tracer studies have suggested that the restrictive barriers(s) are present in the glomerular basement membrane (GBM), the epithelial filtration slits, or both. Recent morphologic and functional tracer studies have indicated that, in addition to size, molecular charge and possibly shape are important determinants in the ultrafiltration process. Negatively charged macromolecules are restricted by the glomerulus more than neutral molecules, while positively charged macromolecules of similar size are filtered in greater amounts. The elements responsible for this specific restriction of polyanions and facilitated transport of polycations are glycoproteins rich in carboxyl groups (sialic acid, dicarboxylic amino acids), which constitute the endothelial and epithelial cell coats and part of the matrix of the glomerular basement membrane. Ultrastructurally, the polyanionic elements of the GBM are localized in its subendothelial and subepithelial layers; the lamina densa, in contrast, appears more neutral, containing most likely a collagen-like glycoprotein.