Plasma albumin restricts capillary water filtration. Accordingly, the glomerular ultrafiltration coefficient is higher in Nagase analbuminemic rats (NAR) than in Sprague-Dawley controls. We investigated whether the glomerular permeability to macromolecules is also enhanced in NAR. SDS-PAGE fractionation of urine proteins showed several bands with molecular masses between 60 and 90 kDa in NAR only. Acute administration of BSA to NAR led to nearly complete disappearance of these proteins from urine, an effect partially reversed when most of the exogenous albumin was cleared from circulation. The fractional clearance of 70-kDa dextran was increased in NAR, indicating a size defect. Binding of cationized ferritin to the glomerular basement membrane was decreased in NAR, suggesting associated depletion of fixed anions. The magnitude of cationic ferritin binding correlated negatively with the fractional clearance of 70-kDa dextran, suggesting that the two abnormalities may share a common pathogenic mechanism. Collectively, these results suggest enhanced glomerular permeability to macromolecules in NAR. Albumin may be necessary to maintain the normal glomerular permselectivity properties.