BACKGROUND: The role of acute phase cytokines generated in the nasopharynx during viral upper respiratory infection (URI) in subsequent development of acute otitis media (AOM) has not been examined. METHODS: We studied 326 virus-positive URI episodes in 151 children aged 6-36 months. Nasopharyngeal secretions collected within 1 to 7 days of URI onset were studied for viruses by conventional and molecular techniques, and for concentrations of IL-1beta, IL-6, and TNFalpha by multiplex enzyme-linked immunosorbent assay. Children were followed up for 28 days to document AOM complication. RESULTS: IL-1beta, IL-6, and TNFalpha concentrations correlated positively with each other (P<0.001). IL-6 and TNFalpha concentrations were higher in males than in females (P=0.01 and 0.02). IL-6 and TNFalpha concentrations were inversely correlated with age (P=0.02 and 0.05). IL-6 concentrations correlated positively with duration of fever (P=0.006) and correlated negatively with the number of days of URI symptoms (P=0.026). Furthermore, IL-6 concentrations were significantly higher during adenovirus and influenza virus URIs as compared with enterovirus and rhinovirus URIs (P<0.01). IL-1beta concentrations were higher during URI episodes with AOM than those without AOM (P<0.001). CONCLUSIONS: We found IL-6 nasopharyngeal secretions concentrations to be higher with adenovirus and influenza infection, and in children with systemic febrile response during URI. However, IL-1beta was found to play a more important role in the development of AOM after URI. Additional studies are needed to further define the role of acute phase cytokines in virus-induced AOM.