We investigated whether percutaneous sensitization with different allergens through barrier-disrupted skin regulates the balance of Th1/Th2 cytokine expression. When mice were sensitized with the typical hapten picryl chloride (PiCl) by a single topical application to intact skin, there was an up-regulation in the lymph nodes (LN) of mRNA expression for the Th1 cytokines IL-2 or IFN-gamma, and for the Th2 cytokine IL-4. In contrast, sensitization with PiCl after barrier disruption of the skin down-regulated the expression of mRNA for IFN-gamma in a tape-stripping number-dependent manner without changing the expression of mRNA for IL-4. When mice were sensitized with house dust mite antigens (MA) by a single topical application to barrier-disrupted abdominal skin, there was a tape-stripping number-dependent up-regulation in the LN of mRNA expression for IL-4 but not for IL-2 or IFN-gamma. In the LN, mRNA for the IL-4-inducible immunoglobulins IgE and IgG1, but not for the IFN-gamma-inducible IgG2a, were up-regulated after sensitization with MA, while all three immunoglobulin mRNA were augmented after PiCl sensitization through intact skin. Antigenic elicitation by a topical application of PiCl in aural skin of mice sensitized through intact skin consistently increased the expression of mRNA for all three cytokines in the challenged skin, whereas elicitation in mice sensitized through barrier-disrupted skin decreased the expression of mRNA for IL-2 and IFN-gamma, but not for IL-4. Antigenic elicitation by subcutaneous injection of MA in aural skin consistently increased the expression of mRNA for IL-4, but not for IL-2 or IFN-gamma in the challenged skin. Infiltration of eosinophils in the dermis was more prominent following elicitation with MA in mice sensitized through barrier disruption than with PiCl in mice sensitized through intact skin. These findings suggest that the percutaneous entry of environmental allergens through barrier-disrupted skin is strongly associated with the induction of Th2-dominant immunological responses, as is seen in atopic dermatitis.