We previously have demonstrated impaired pneumococcal polysaccharide IgG antibody responses in children immunosuppressed following cardiac transplantation in early childhood. We have further characterized the antibody defect. To further investigate the production of antibody, antipneumococcal polysaccharide (PPS) specific IgM, IgG, IgG subclasses, and IgA were measured in postvaccination sera by enzyme-linked immunosorbent assay. Two groups were studied: posttransplant children who made pneumococcal antibody in vivo following natural exposure or PPS immunization (R) and those with an impaired response (NR). There was no difference in IgM or IgA levels between R and NR. IgG and IgG2 levels were higher in R than NR (P = 0.002), even after adsorption of nonspecific common cell wall antigen antibody. Differences in anti-pneumococcal antibody levels suggest that immunoglobulin isotype switching from IgM to IgG and particularly IgG2 is impaired in patients immunosuppressed at a young age. These findings confirm data regarding the effect of immunosuppressive agents derived from animal models in humans.