Abnormal immune cell (especially T-cell) accumulation in the airways is characteristic of patients with asthma. We submit that this immune cell behavior (a manifestation of adaptive immunity) is regulated in turn by the primary response of airway epithelial cells (a critical component of innate immunity), and this cell-cell interaction is especially relevant in the host response to respiratory viral infection. We have presented evidence that a subset of epithelial immune-response genes may be critical for antiviral immunity and may contribute to aberrant immune cell activation in asthma. Thus, paramyxoviral infection and asthma may share a propensity to activate a network of epithelial immune-response genes that are part of the innate immune response.24-26 However, these studies did not directly address the issues of the underlying mechanisms for chronicity and susceptibility to the asthma phenotype. Our most recent results extend this concept by analyzing whether a persistent antiviral response can drive the asthma phenotype, at least experimentally. In that regard, we have established the capacity of a single, transient paramyxoviral infection to permanently change epithelial behavior and airway reactivity in a pattern that is remarkably similar to one in asthma and that overlaps with other hypersecretory diseases. Furthermore, this chronic phenotype can be genetically segregated from the acute antiviral response in mice. The teleology of this chronic response is uncertain, but perhaps it represents an evolving but maladaptive attempt to improve antiviral host defense. Similarly, we speculate that these phenotypes (ie, airway hyperreactivity and goblet cell hyperplasia) may ordinarily be beneficial in host defense. In the setting of allergen exposure, several gene products appear to regulate goblet cell hyperplasia, fitting a paradigm in which Th2 products (eg, IL-4, IL-5, IL-9, and IL-13) may up-regulate the response, while Th1 products (eg, IFN-γ and IL-12) down-regulate the response. Further studies will be required to precisely identify the genes that are responsible for epithelial remodeling and chronic hyperreactivity in response to paramyxoviral infection, but the lack of IFN-γ-dependent regulation in this setting implies already that the viral pathway is distinct from the ones driven by allergen. Indeed, the results raise the possibility that primary paramyxoviral infection in the proper genetic background may lead to the chronic dysfunction of host cell behavior that overlaps with but does not depend on allergy.