Recently we have demonstrated that, besides V gamma 5(+) gamma/delta TcR(+) T cells (V gamma 5(+) gamma/delta T cells), V gamma 5(-) gamma/delta TcR(+) T cells (V gamma 5(-) gamma/delta T cells) are also present in murine skin, In the present study, to characterize the functional differences between these two different cutaneous gamma/delta T cells we examined the expression pattern of E-cadherin and its two integrins, After co-culturing of Ly-5(+) epidermal cells and migrating cells from organ-cultured murine skin with cutaneous stromal cells, we could expand V gamma 5(+) gamma/delta T cells and V gamma 5(-) gamma/delta T cells, respectively, Flow cytometry demonstrated that cultured V gamma 5(+) gamma/delta T cells expressed E-cadherin, but V gamma 5(-) gamma/delta T cells did not, This difference in E-cadherin expression was also observed in freshly isolated V gamma 5(+) and V gamma 5(-) gamma/delta T cells, On the other hand, both V gamma 5(+) and V gamma 5(-) gamma/delta T cells expressed the alpha chain of the vitronectin receptor, but did not express the alpha 4 integrin, Of these two cutaneous gamma/delta T cells, only V gamma 5(+) gamma/delta T cells adhered to murine keratinocyte cell line, PAM 212 cells, Unexpectedly, however, the adhesion of E-cadherin-expressing V gamma 5(+) gamma/delta T cells to PAM 212 cells was not inhibited by anti-E-cadherin antibody, which effectively abrogated the adhesion of Langerhans cells to PAM 212 cells, These distinct phenotypic and functional characteristics in the subsets of cutaneous gamma/delta T cells may suggest that they reside in different locations in the skin to play different functional roles in skin immunophysiology.