To critically evaluate the clinical utility of determining specific proteins in patients with extensive proteinuria, we used immunonephelometric methods to measure albumin, transferrin, IgG, and alpha 2-macroglobulin in serum and in 24-h urine specimens from 37 children with idiopathic nephrotic syndrome. Renal biopsy demonstrated minimal change disease (I) in 15, focal glomerulosclerosis (II) in 15, and membranoproliferative glomerulonephritis (III) in seven patients. A three-group nonparametric rank test and three-group discriminant function analysis of the protein excretion and clearances of the four proteins we measured revealed significant differences in the excretion of IgG and the clearance of alpha 2-macroglobulin among the three groups of patients (p less than 0.05). Only patients with III had low serum complement C3 concentrations. Patients with I or II were best discriminated by differences in the excretion of transferrin and IgG, the clearance of alpha 2-macroglobulin, and the selectivity index (the clearance ratio of IgG/transferrin). These data indicate that measurement of specific urinary proteins and selectivity determinations may be helpful in predicting the type of histopathology and the prognosis of nephrotic children who have normal complement concentrations.