Murine dendritic epidermal T cells (DETC) were recently reported to express T-cell receptor (TCR)-γ/δ chains. In a search for the human equivalent of these cells, we tested normal and lesional skin with MoAb which react with the TCR-γ/δ heterodimer. We performed indirect immunofluorescence (IF) on epidermal sheets, and alkaline- phosphatase-anti-alkaline-phosphatase complex (APAAP) on epidermal cell smears. Frozen skin sections from normal skin and various cutaneous lymphocyte infiltrates were also studied. A few CD3+ T lymphocytes were consistently found in normal epidermis. Most of these cells appeared to be TCR-α/β+, and some CD4+ or CD8+. On epidermal sheets and cell smears, only a very small TCR-γ/δ+ cell population was visualized (less than 0.1% of the total). On normal skin sections, we observed 0 to 3 γ/δ+ cells per section. When present, they were often located in the epidermal basal layer, and were round or dendritic. Double immunolabeling revealed that γ/δ+ cells differed from CD1+ Langerhans cells, and that they had a similar phenotypic pattern as γ/δ+ peripheral lymphocytes (PBL): CD2+, CD3+, CD4-, and CD8-. Immunostaining from various inflammatory skin lesions showed that the dermal infiltrates included CD3+ T lymphocytes but virtually no γ/δ+ cells. Only a few γ/δ+ cells were found in some end-evolutive infiltrates. Taken together, these results strongly suggest that normal human epidermis occasionally harbors TCR-γ/δ complex bearing lymphocytes, which constitute a small fraction of the CD3+ cutaneous T lymphocytes. Despite their common location and TCR expression, there is presently no evidence that these human cutaneous TCR-γ/δ bearing T cells are the equivalent of murine DETC.