Uncharged dextrans of graded size (28–60 Å) were used to evaluate glomerular barrier size selectivity in 13 nephrotic patients with diffuse proliferative lupus nephritis. Transglomerular sieving was enhanced selectively for dextrans of > 46 Å radius when the nephritis was active and restored towards normal by immunosuppressive therapy. A mathematical model of hindered solute transport through a porous membrane revealed these findings to reflect the prevalence in the glomerular barrier of a subset of enlarged, nondiscriminatory pores. Although few in number, such enlarged pores accounted for both the magnitude and composition of observed proteinuria. We infer that impaired barrier size selectivity underlies the proteinuria that attends lupus nephritis, and that impairment of barrier charge selectivity need not be invoked in this circumsta