The formation of glomerular ultrafiltrate is dependent on the interplay of glomerular pressures and flows as well as the intrinsic permselectivity properties of the glomerular capillary wall. These intrinsic permeability properties serve to exclude macromolecules from the urinary space, based on size as well as net molecular charge discrimination. Neutral dextrans with molecular radii less than 20 A cross the glomerular wall without measurable restriction, whereas dextrans with radii greater than 42 A are almost completely barred. For any given size, negatively charged macromolecules are restricted to a greater extent than neutral molecules. Additionally, positively charged molecules are enhanced in their ability to cross the glomerular wall compared to similarly sized neutral polymers. The concept of a charge barrier, due to fixed negative charges within the glomerular wall, is also supported by morphological studies. Glomerular injury, leading to proteinuria, has been associated with loss of the charge-selective properties of these capillaries. Loss of glomerular fixed negative charges may also result in the foot process fusion and mesangial cell dysfunction often observed in proteinuric states.