Otitis media is a significant worldwide health problem, with significant morbidity related to frequent illness in early childhood, leading to communicative disorders and hearing loss in some affected children. Respiratory virus infections appear to play a major role in the pathogenesis of otitis media. Streptococcus pneumoniae is the principal bacterial pathogen infecting the middle ear of children with otitis media, and it is well known that disease due to pneumococcus often complicates other respiratory viral infections. The pathogenesis of pneumococcal otitis media during infection with influenza, parainfluenza and respiratory syncytial viruses will be investigated in chinchillas harboring Streptococcus pneumoniae in their upper respiratory tract. Influenza A virus strains of differing virulence in humans, including a cold-adapted vaccine strain, respiratory syncytial virus and parainfluenza viruses will be studied for their effects on respiratory cilia, adherence of pneumococci to epithelial cells, eustachian tube ventilation, and peripheral blood and tissue polymorphonuclear leukocyte function. A study will be performed in children with upper respiratory viral infection and paracentesis confirmed acute otitis media to measure the effect of specific, laboratory documented respiratory virus infection on eustachian tube and polymorphonuclear leukocyte function. This human study will provide important data for correlating observations made in the animal model with the human disease. Susceptibility of virus-infected animals to pneumococcal disease will be compared among the virus strains, and rates of clearing pneumococci from the nasopharynx will be compared. The influence of prior colonization with pneumococcus and of active immunization with attenuated influenza virus on the subsequent susceptibility to pneumococcal otitis media will be investigated. This investigation will provide important new information concerning the role of local and systemic host defense mechanisms which protect against pneumococcal disease. Specific defects in host defense produced by respiratory viruses will be described. Because the animal model closely parallels respiratory virus infection and pneumococcal disease in humans, the results of this investigation will suggest approaches for treating and preventing pneumococcal otitis media in humans.