We found that mechanical injury to mouse skin, which can be caused by tape stripping, results in rapid induction of IL-10 mRNA. IL-10^–/– mice were used to examine the role of IL-10 in a mouse model of allergic dermatitis induced by epicutaneous (EC) sensitization with OVA on tape-stripped skin. Skin infiltration by eosinophils and expression of eotaxin, IL-4, and IL-5 mRNA in OVA-sensitized skin sites were severely diminished in IL-10^–/– mice. Following in vitro stimulation with OVA, splenocytes from EC-sensitized IL-10^–/– mice secreted significantly less IL-4, but significantly more IFN-γ, than splenocytes from WT controls. A similar skewing in cytokine secretion profile was observed in the splenocytes of IL-10^–/– mice immunized intraperitoneally with OVA. IL-10^–/– APCs skewed the in vitro response of OVA T cell receptor (TCR) transgenic T cells towards Th1. Examination of the Th response of WT and IL-10^–/– mice immunized with OVA-pulsed WT or IL-10^–/– DCs revealed that both DCs and T cells participate in IL-10 skewing of the Th2 response in vivo. These results suggest that IL-10 plays an important role in the Th2 response to antigen and in the development of skin eosinophilia in a murine model of allergic dermatitis.