Background: Deficiencies of serum Ig of the IgG isotype typically predispose individuals to recurrent infections in some but not all cases. Patients with large deletions of the Ig heavy chain genes are free of recurrent and severe infections. Objective: We sought to determine a mechanism of immunologic compensation that would possibly explain the reason for this patient's paucity of infection despite lacking several classes of serum Ig. Methods: The patient is a 50-year-old white man. Serum Ig levels and specific antibody titers were measured by using various methods, including nephelometry, enzyme immunoassay, and radial immunodiffusion. The status of the Ig heavy chain genes was examined by means of Southern blotting of genomic DNA isolated from EBV-transformed B cells. Results: The patient's serum lacked detectable IgG1, IgG2, IgG4, and IgA1 levels. Southern blot analysis demonstrated a large heavy chain constant (C) region gene deletion that included Cγ1, Cα1, ψCγ, Cγ2, and Cγ4. Antibody responses to capsular pneumococcal and hemophilus polysaccharide antigens were essentially absent. However, IgG3 antibodies against the protein antigen tetanus toxoid were present, Relatively high antibody titers were found against pneumococcal surface proteins as well. Conclusion: We conclude that our patient's relative freedom from serious infection may be as a result of production of IgG3 antibodies to pneumococcal capsular proteins.