Dendritic epidermal T cells (DETC) are CD45⁺, Thy-1⁺, CD5⁻, CD8⁻, CD4⁻ murine lymphocytes that express surface-bound CD3 antigens associated with T cell receptor γ/δ heterodimers. Using epidermal cells greatly enriched for DETC and depleted of Langerhans cells, we found that DETC have growth requirements quite different from those of accessory cell-depleted lymph node and splenic T cells. Although the latter cells strongly proliferate in response to phorbol myristate acetate (PMA) + ionomycin, DETC, when exposed to interleukin-1 (IL-1), interleukin-3 (IL-3), concanavalin A (ConA), PMA, and ionomycin used either alone or in combination, do not exhibit significant mitotic activity. Recombinant interleukin 2 (rIL-2), albeit ineffective by itself, leads to vigorous proliferation of DETC when used with either ConA or PMA + ionomycin + IL-1. In contrast, the combination of PMA and recombinant interleukin-4 (rIL-4), which triggers growth of lymph node T cells, does not induce proliferation of DETC. Although a portion of proliferating DETC expressed CD8 antigens, essentially none bore detectable amounts of surface-bound CD4 or CD5 antigens, or both. Continuing stimulation of primary DETC cultures with lectin/lymphokine-rich media results in the propagation of cells with the essential phenotypic features of resident DETC.