The epidermis of mice contains, in addition to Langerhans cells, a second dendritic population that is Thy-1+/CD3+ CD4-/CD8-/T-cell receptor-Vγ3/Vδ1+. These dendritic epidermal T cells (DETC) are now thought to comprise one element in the family of epithelial tissue-resident γδT cells. In the present study, DETCs were examined for their expression of mRNA for cytokines, using a reverse transcription-polymerase chain reaction. Freshly isolated Thy-1+ epidermal cells constitutively expressed mRNA for γ-interferon, but not IL-2. Within 24 h after stimulation with Con A, these cells then expressed mRNA for γ-interferon and IL-2, but not IL-4. The rapid onset of expression of mRNA for IL-2 occurred exclusively within the Thy-1+ population, and in a Con A-dependent fashion. When freshly isolated epidermal cells were first stimulated with Con A and then expanded in bulk with rIL-2 for 20–24 d, cells expressing IL-4 mRNA then emerged, upon secondary stimulation with Con A. These “short-term” DETC lines also expressed mRNA for IL-2, interferon-γ, IL-1α, IL-3, IL-6, IL-7, tumor necrosis factor α and β, and granulocyte macrophage-colony stimulating factor. Interestingly, mRNA for IL-4 and IL-6 was no longer detected in long-term (>1 year) DETC lines 7–17 and 12–12. In addition, one line (7–17) maintained IL-3 mRNA expression, whereas another (12–12) had lost this capacity. These results emphasize the concept that, as resident cells in epidermis, DETCs exhibit several different immunorelevant activities, and the heterogeneity in cytokine mRNA profiles suggests that DETCs may divide into functional subsets.