BACKGROUND: Acute otitis media (AOM) is a frequent complication of viral upper respiratory tract infection (URI). We hypothesized that the severity of nasopharyngeal cellular injury during URI, as measured by lactate dehydrogenase (LDH) concentrations in nasopharyngeal secretions (NPSs), is related to AOM complication. METHODS: LDH concentrations were determined in NPS samples (n = 594) that were collected at the initial visit for URI from 183 children who were followed for the development of AOM. A subset of NPS samples (n = 134) was analyzed for interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha concentrations. RESULTS: AOM complication was independently predicted by LDH concentrations (median mU/ml with AOM = 2,438 vs. without AOM = 1,573; estimate = 0.276; P = 0.02). LDH effect on AOM development was highest during the first 4 d of URI. LDH concentrations were higher in URIs due to adenoviruses, bocaviruses, and rhinoviruses as compared with virus-negative samples (P < 0.05). There was a positive correlation between concentrations of LDH and all cytokines (P < 0.001). CONCLUSION: LDH concentrations in NPS are positively associated with AOM risk, suggesting that the severity of nasopharyngeal inflammatory injury during URI contributes to the development of AOM and that reduction of inflammatory injury may reduce the risk for AOM.