Thus, in our studies, we demonstrated that CpG ODN are effective in preventing the development of eosinophilic airway inflammation and bronchial hyper-reactivity in a murine model of asthma. Antigen-associated elevation of serum IgE levels is also suppressed. CpG ODN, administered in conjunction with antigen, is also effective in down-regulation of established Th2 responses. This protection is neither murine strain-dependent nor model-dependent. Although these effects of CpG ODN are associated with the induction of the Th1 cytokines IFN-gamma and IL-12, neither cytokine is absolutely required for the protection. These results suggest that CpG ODN may be an effective immunomodulatory agent in the treatment, and possibly prevention, of asthma.