This study explores the pathogenesis of otitis media with effusion (OME) and assesses the contribution of the various risk factors including infection, especially viral, allergy and immune competence. Experimental URI using rhinovirus (RV-39) and influenza A virus (IFA) were induced in normal susceptible human volunteers with and without a history of allergic rhinitis. Eustachian tube dysfunction was induced in 70 to 80% of infected subjects for both viruses with OME in 3% of RV-39 and 20% of IFA infected subjects. Enhanced serum IgE synthesis and WBC histamine release was documented in allergic but not in non-allergic subjects; whereas both groups had enhanced cytokines (IL-6, 8 and 10) in nasal secretions. The effect of Respiratory Synctial Virus (RSV) on upper and lower airway function is now being explored. Two cohorts have been experimentally inoculated and data is currently being analyzed. Preliminary results from one cohort shows that RSV provoked upper airway pathophysiology which extended to otologic parameters, in experimentally infected subjects.