This project will explore relationships between intranasal inoculation of Streptococcus pneumoniae with and without influenza A virus, a variety of host defenses and the development of pneumococcal pneumonia, bacteremia and otitis media. Humoral immune response to S. pneumoniae and influenza A virus will be measured in serum and effusions using radio-immunoassay and ELISA to quantify type-specific pneumococcal antibody, and a complement fixation test will be used to measure influenza antibody. Serum pneumococcal opsonic activity will be measured using a phagocytic assay. Polymorphonuclear leukocyte chemotaxis, chemiluminescene and microbicidal activity will be measured using peripheral blood PMNs obtained after inoculation. Lung, middle ear, eustachian tube and nasopharyngeal histopathology will be described. Tympanometry will be employed to measure middle ear pressures after inoculation. The capacity of pneumococci to adhere to epithelia cells of the nasopharynx in vivo and in vitro will be measured after inoculation.