We have recently used graded dextrans as tracers to investigate glomerular permeability in normal rats (1) in order to determine which structure in the glomerular capillary wall, the basement membrane or the epithelial slits, represents the primary filtration barrier to macromolecules . Three dextran fractions of specified mol wt (40,000, 62,000, and 125,000) were prepared which bracket the size of albumin, the molecule effectively retained by the normal glomerulus. When injected intravenously into rats, the dextran fractions behaved as predicted in that they were extensively filtered, filtered in small amounts, and extensively retained, respectively . In all three cases dextran particles were found initially in high concentration in the capillary lumen and in the subendothelial portions of the basement membrane but there was a sharp drop in their concentration at this level, i.e., between the inner looser portions of the basement membrane and its outer more compact portions . With the two largest fractions accumulation of particles occurred against the basement membrane in mesangial regions with time, but no accumulation was ever seen with any of the fractions in the epithelial slits or against the slit membranes . Therefore, we concluded that the results obtained with dextrans, like those obtained previously using ferritin as a tracer (2, 3), identify the glomerular basement membrane as the main barrier to the passage of macromolecules of the size of albumin in the normal glomerulus.In order to extend these observations we have carried out similar studies on animals with experimental nephrosis (induced with an aminonucleoside of puromycin) . Nephrotic animals represent an interesting situation in which to study glomerular permeability since they show albuminuria due to increased leakage of albumin by the glomerulus, accompanied by profound changes in the glomerular capillary wall (cf. 4) : the usual epithelial foot process organization is lost with a concomitant reduction in the number of epithelial filtration slits, the epithelial cells become filled with protein absorption droplets (i.e., phagosomes and lysosomes), and the basement membrane appears thinner and less compact in some regions.