On the basis of initial evidence, infl ammation has been proposed as a possible cause or driving force of avian infl uenza (H5N1). However, components of the infl ammatory response might even be benefi cial. To address these possibilities, we need to determine whether infl ammation in avian infl uenza is an early event and a manifestation of innate immune response. If it is, some of the mediators of innate immune response, such as cytokine/chemokine levels, can be included in the evaluation of the potency of candidate vaccines. Further humoral response as a correlate for protection can be fi ne-tuned by determining the titer and isotype of antibody after vaccination. Several issues concerning vaccine effi cacy are unresolved: What are the consequences of vaccination for existing infl uenza (H5N1) infection, the extent of serologic cross-reactivity between the most closely related types of the virus, and the role in clinical protection? Vaccine administration may provide some therapeutic effects for infected persons who have not yet made an immune response but provide none for those with persistent infection associated with measurable humoral immunity.