The pathophysiology of allergic diseases involves an intricate network of molecular and cellular interactions. Elevated levels of serum IgE- and TH2 cytokine-associated eosinophilic inflammation characterize allergic diseases and provide potential targets for immunomodulation. Recent evidence that antigen-induced allergic responses can be modulated in rodents by mucosal transfer of TH1-cytokine genes or by immunization with plasmid DNAs encoding the sensitizing antigens suggests promising new prophylactic or therapeutic approaches. Innovative research in mapping the regulatory pathways that typify the atopy network will provide a deeper understanding of the molecular mechanisms underlying these diseases and facilitate the design of more specific and efficacious modulation strategies.