Unchanged dextrans of graded size (28-60 A) were used to evaluate barrier size-selectivity in 56 proteinuric patients with diabetic glomerular disease. Transglomerular sieving was enhanced selectively for dextrans of greater than 46 A radius. A mathematical model of hindered solute transport through a porous membrane showed that this finding reflected the development in the glomerular barrier of a subset of enlarged, non-discriminatory pores. Although few in number, these enlarged pores accounted for both the magnitude and the composition of the observed proteinuria. We conclude that impaired barrier size-selectivity underlies the proteinuria of diabetic glomerular disease, and that impairment of barrier charge-selectivity need not be invoked in this circumstance.