In this study, glomerular sieving coefficients (() of Ficoll (a highly cross-linked, nearly spherical polysaccharide) were measured in vivo, in rats with PAN nephrosis vs. control and compared to those obtained in a prior study, using rigid globular proteins as molecular probes. (Tencer et al. Kidney Int. 1998; 53:709-15). In anesthetized rats, ureters were cannulated for urine sampling and Ficoll-70/400 was given as an iv-bolus, followed by an infusion. ( for FITC-Ficoll were determined from a 5 min urine collection and a midpoint plasma sample. Size separation of Ficoll in urine and plasma were achieved by size exclusion HPLC. ( for albumin and IgG where obtained by measuring their plasma-to-filtrate ratio and prox. tubular reabsorbtion was inhibited with lysine. GFR was assessed with inulin & Cr-EDTA. The GFR decreased markedly with PAN, from 0.983 ± 0.17mL/min (mean±SE) in controls to 0.109 ± 0.0028. ( for Ficoll36Å (cf albumin) increased 3-fold with PAN, from 8.25x10-2 ± 1.8x10-2 to 2.45x10-1 ± 1.38x10-2. However, ( for Ficoll55Å (cf IgG) increased 55-fold in the PAN group, from 3.9x10-4 ± 3.39x10-5 to 1.75x10-2 ± 1.28x10-3. Comparable ( for albumin in control and PAN groups were 3.31x10-4 (1.17x10-4-9.21x10-4) vs.5.91x10-2 (3.20x10-2-3.21x10-1), respectively (180-fold increase). An identical increase in ( was noted for IgG. The small pore radius increased after PAN (to 59.46 ± 0.56Å from 46.53 ± 0.50Å), while the large pore radius did not change significantly. Their number, however, increased 90 fold. In conclusion, in PAN nephrosis, there was a marked increase in the transport of Ficoll molecules of SE-radii >60Å, largely compatible with that seen for proteins traversing large pores.