BACKGROUND: One potential mechanism by which respiratory viruses trigger illness and complications is via the local elaboration of inflammatory mediators. OBJECTIVE: To determine whether there is an increase in local leukotriene C4 (LTC4) levels during experimental infection with influenza A virus (FLU), rhinovirus (RV), or respiratory syncytial virus (RSV). METHODS: Healthy adults were intranasally inoculated with a safety-tested strain of FLU (n = 29), RV (n = 16), or RSV (n = 21). Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed before and then daily after challenge. Lavage samples were submitted for viral culture and assayed for LTC4 levels by radioimmunoassay. Serum antibody titers to the challenge viruses were assayed at baseline and 21 days after challenge. RESULTS: All subjects were infected as evidenced by viral shedding and/or seroconversion. Following infection, significant increases (P < 0.05 by analysis of variance) in LTC4 levels were measured for each virus. Furthermore, there was a temporal association between the local LTC4 levels and the development of illness. CONCLUSIONS: The results of this study, which used an adult experimental model, demonstrate elevations in locally produced LTC4 during respiratory infection with FLU, RV, and RSV. Future studies using antileukotriene agents may help elucidate the precise role of leukotrienes in mediating disease expression.