The accuracy of using the initial response to prednisone to identify children with minimal glomerular changes has been assessed in a prospective study of children between 12 weeks and 16 years of age with the primary nephrotic syndrome. The results indicate that, as generally held, the likelihood is quite high, although not 100%, that a child with the primary nephrotic syndrome who responds during eight weeks of initial intensive steroid treatment has MCNS. Prognosis in these patients can be considered to be very favorable and renal biopsy need not be done unless indicated by the subsequent clinical course. However, the prediction that a patient who fails to respond has a glomerular lesion other than MCNS would be incorrect in about one-fourth of all patients with the primary nephrotic syndrome, and in as many as one-half of patients less than or equal to 6 years of age. For these patients, predictions concerning prognosis should be withheld until a renal biopsy provides a histopathologic diagnosis.