The V gamma 6/V delta 1(+) cells, the second murine gamma delta T cell subset to arise in the thymus, express a nearly invariant T cell receptor (TCR), colonize select tissues, and expand preferentially in other tissues during inflammation. These cells are thought to help in regulating the inflammatory response. Until now, V gamma 6/V delta 1(+) cells have only been detectable indirectly, by expression of V gamma 6-encoding mRNA. Here, we report that 17D1, a monoclonal antibody, which detects the related epidermis-associated V gamma 5/V delta 1(+) TCR, will also bind the V gamma 6/V delta 1(+) cells if their TCR is first complexed to an anti-C delta antibody. Features of this special condition for recognition suggest the possibility that an alternate structure exists for the V gamma 6/V delta 1 TCR, which is stabilized upon binding to the anti-C delta antibody. Using the 17D1 antibody as means to track this gamma delta T cell subset by flow cytometry, we discovered that the response of V gamma 6/V delta 1(+) cells during inflammation often far exceeds that of other subsets and that the responding V gamma 6/V delta 1(+) cells display a strikingly uniform activation/memory phenotype compared with other gamma delta T cell subsets.