Adult mouse epidermis contains a population of dendritic,Thy‐l⁺,CD3⁺,CD4⁻, CD8⁻ and T cell receptor (TcR) Vγ3/Vδ1⁺ leukocytes termed dendritic epidermal T cells (DETC). DETC isolated from skin and placed into culture will proliferative vigorously in response to T cell mitogens and T cell growth factors. In the present study, we examined whether DETC can be activated in situ by modulating their epidermal environment. Ear skin of CBA mice was painted with the chemical irritant, croton oil, and the epidermal cells (EC) isolated from such sites were then tested for proliferative responses to exogenous interleukin‐2 (IL‐2), in the absence of added mitogens. Cells from croton oil‐treated skin showed marked IL‐2 responsiveness, whereas cells from phosphate‐buffered saline‐treated skin failed to proliferate. IL‐2 responses were seen as early as 2 days after croton oil treatment and peaked between days 5 and 10. γδ TcR‐bearing cells, most likely resident DETC, were the major population to respond to IL‐2, since depletion of γδ TcR⁺ cells, but not γδ TcR⁺ cells, abolished that responsiveness, and since γδ TcR⁺ cell numbers increased markedly in the cultures that contained added IL‐2. These results indicate that DETC in normal skin, which are at a state of rest, may be activated when their residential epidermal environment is disrupted externally. This process of DETC activation may be a critical step in the maturation of DETC into effector leukocytes in vivo.