We studied alcian blue (AB) binding to red blood cells (RBC) [ABRBC] in 89 children and adults with a variety of glomerular diseases. ABRBC was significantly reduced in the group as a whole when compared with healthy controls (P < 0.001). A moderate correlation between the degree of proteinuria and ABRBC was detected in the children with renal disease (r = 0.43, P < 0.001), but not in adult patients. A significant reduction in ABRBC was detected in 30 of the above children who had Steroid Responsive Nephrotic Syndrome (MCNS) compared to their controls (40.57 +/- 16.6 v. 75.09 +/- 7.81, P = 0.001). A similar decrease from normal values was observed in other childhood glomerular diseases: focal glomerulosclerosis, post-streptococcal glomerulonephritis, membranous nephropathy (52.31 +/- 26.07 v. 79.44 +/- 5.88, P = 0.001). Mean ABRBC was lower in MCNS than other histological groups (P = 0.0518). ABRBC was age-dependent (r = -0.399, P < 0.02). These findings provide further indirect evidence of the relative roles of charge and size selective filters in glomerular basement membrane (GBM) in renal diseases, and suggest that depletion of anionic charge may be a major cause of proteinuria in MCNS.