OBJECTIVE To evaluate the isotype and IgG subclass distribution of anti-pneumococcal antibodies and response to polysaccharide vaccination in otitis prone children. METHODS IgG1, IgG2 and IgA antibodies to pneumococcal serotypes 3, 4, 6B, 9V, 14, 19F and 23F were determined in otitis prone children and in an age-matched healthy control population. Patients were immunized with a 23-valent pneumococcal polysaccharide vaccine. The antibody response was measured 4 weeks later. RESULTS Geometric mean IgA and IgG2 antibody levels for all seven pneumococcal serotypes tested were significantly lower in otitis prone children than in the control population. After immunization, there was no significant increase in geometric mean IgG2 anti-serotype 6B, 19F and 23F pneumococcal polysaccharide (weak immunogenic), but also no increase for IgG2 anti-serotype 4 and 14. Post immunization IgG2 antibody titers for serotypes 6B, 9V and 19F even remained below titers of non-vaccinated controls. Nine out of 29 otitis prone children were colonized nasopharyngeally with Streptococcus pneumoniae during the time of vaccination; these children had an even more severely impaired systemic antibody response. CONCLUSIONS Otitis prone children, while having normal IgG1 antibody levels, have low IgG2 and IgA anti-polysaccharide antibody levels and fail to respond in these subclasses upon vaccination with pneumococcal polysaccharide vaccine.