The renal clearance of dextran and protein of different molecular sizes has been measured in 42 proteinuric patients with diabetes and glomerulonephritis. In both patient groups the fractional low molecular (radii 3.0-3.6 nm) dextran clearances were significantly decreased whereas the fractional high molecular (radii 5.1-7.8 nm) dextran clearances were increased as compared with the controls. A porosity/charge index was constructed by calculating the ratio of fractional clearances of neutral to anionic macromolecules (theta D3.6/theta ALB, theta D5.1/theta IgG). In diabetic patients the relation between the fractional clearances of neutral and anionic macromolecules was dependent on glomerular filtration rate. It seems likely that the altered glomerular permeability in diabetic nephropathy is associated with a decrease of charge as renal function deteriorates. In glomerulonephritis the process is different and there is a high degree of variation from case to case.