CpG-oligodeoxynucleotide (CpG-ODN) plays a critical role in immunity via the augmentation of Th1 and suppression of Th2 responses. We examined here the effect of CpG-ODN on the immune response to an antigen applied to tape-stripped mouse skin by evaluating the production of cytokines and Ig isotypes. Confocal laser scanning microscopy revealed that the model antigen, OVA, and CpG-ODN easily penetrated the tape-stripped skin. Co-administration of CpG-ODN and OVA to the disrupted skin elicited an antigen-specific Th1-predominant immune response and enhanced the production of Th1-type cytokines, IL-12 and IFN-gamma. On the other hand, the production of a Th2-type cytokine, IL-4, was drastically suppressed. Cytokine production was supported by the expression of mRNA in the draining lymph node. In terms of antigen-specific antibody production, the level of IgG2a which is regulated by IFN-gamma was increased by CpG-ODN, but IgE production regulated by IL-4 was suppressed. Furthermore, administration of CpG-ODN via the skin drastically attenuated the production of IgE in mice undergoing IgE-type immune response. Administration of CpG-ODN through the skin may shift the immune response from Th2 to Th1-like response. These results suggested that administration of CpG-ODN via skin is a simple strategy for patients with diseases like AD, which is characterized by Th2-dominated inflammation.