Effect of colloid volume expansion on glomerular barrier size–selectivity in humans. Colloid volume expansion magnifies proteinuria in subjects with the nephrotic syndrome. To elucidate this phenomenon, we performed differential solute clearances prior to and following infusion of hyperoncotic albumin in 21 nephrotic subjects and seven healthy controls. Urinary excretion rate and fractional clearance of albumin (radius = 36 Å) and immunoglobulin G (radius = 55 Å) increased significantly in nephrotic subjects. However, urinary albumin excretion rate was unchanged in controls. The fractional clearances of dextrans of broad size distribution (radii = 28 to 58 Å) were markedly altered in both groups following albumin infusion. A heteroporous model which depicts the major portion of the glomerular capillary wall as an isoporous membrane (pore radius ˜55 Å) and the minor portion as a non-discriminatory shunt, revealed the latter to be much more prominent in nephrotic subjects than in controls, and to be enlarged further following albumin infusion. By contrast no increase in pore size of the non-shunt pathway occurred in either group. We infer that enhancement of a pre-existing defect of glomerular size–selectivity in nephrotic subjects accounts, in large part, for exaggerated proteinuria in the colloid volume–expanded state. Increases in glomerular perfusion rate and pressure associated with plasma hypervolemia may mediate this alteration in glomerular membrane–pore structure.