The recent and growing problem of bacterial resistance to common antibiotics has generated great interest in different methods for prevention of infections. The treatment of the pathogens causing upper airway infections and especially acute otitis media (AOM) is especially interesting in this context because these infections are a common cause of prescription of antibiotics all over the world. Both in AOM and recurrent AOM, Streptococcus pneumoniae, the most frequently occurring bacterium is isolated in 30-50% of all AOM attacks. In the last decade, multiresistant S. pneumoniae have emerged as a major problem. Thus, it is important to explore possibilities that immunization may protect against pneumococcal OM. In a well-defined animal model using Sprague-Dawley rats, we have investigated the effects of different routes of immunization with different antigens and whole cells. Together with otomicroscopical evaluation of middle ear (ME) status, samples for bacterial cultivation as well as for studies of histopathological changes have been collected. Antibody titers have been followed during and after pneumococcal AOM by an enzyme-linked immunosorbent assay (ELISA) method.