To determine whether the hypogammaglobulinemia of childhood nephrotic syndrome is characterized by symmetric depression of the IgG subclasses, the authors compared the IgG subclass concentrations in nephrotic patients in relapse versus remission. The authors used a highly sensitive monoclonal antibody-based enzyme immunoassay that allows quantitation with comparable precision of all four subclasses. They analyzed 28 sera obtained from 22 nephrotic patients during relapse (n = 16) and/or remission (n = 12). The mean ages of the two groups were similar. IgG1 and IgG2 were significantly decreased during relapse compared with remission, whereas IgG3 and IgG4 were not significantly different. This pattern of asymmetric depression of IgG subclasses supports a cause other than urinary losses in the pathogenesis of this abnormality.