Because we have noted discordant results in the measurement of IgG subclass concentrations by means of a widely available commercial radial immunodiffusion (RID) kit in comparison with an enzyme-linked immunosorbent assay (ELISA) developed at the Centers for Disease Control (CDC), we conducted in a blinded manner a comparison of the two assays, using sera from 48 healthy children. The correlation coefficients between the assays were 0.92, 0.82, 0.93, and 0.86 for the IgG1, IgG2, IgG3, and IgG4 assays, respectively. However, the RID assay assigned lower values for IgG1 and IgG4 determinations than the ELISA did. Furthermore, the "normal lower range values" provided by the RID assay were higher for each IgG subclass. When the sera from the healthy control subjects were analyzed with the RID assay, 12 (25%) of 48 subjects had values below the normal range for at least one subclass measurement. In contrast, with the CDC ELISA, all values were within the 95% confidence limits determined for the CDC ELISA. We suggest that age-specific normal limits be established with the use of sera from many healthy subjects for any assay measuring IgG subclass concentrations. As new groups of immunodeficiencies are defined and potential therapies are advocated, careful attention to assay standardization will result in a clearer delineation of these disease groups and of their response to treatment.