E-Sdectin is an inducible adhesion protein expressed by endothelial ceils and recognized by lenkocytes duringtheir extravasation from the blood into inflamed tissues. Originally, E-sdectin was defined as a mydoid ceil-specific adhesion protein, but recent studies have shown it to be recognized by human lymphocytes as well. These lymphocytes represent a memory T cell subset and have been shown to express the HECA-452 carbohydrate epitope (CLA+ lymphocytes). We extend these findings and show that ruminant γ/δ T cells bind E-sdectin as well; and we provide preliminary evidence that this interaction is mediatedby a novel glycoprotein receptor on the lymphocyte. Unlike conventional T ceils (α/β T cells), γ/δ T cells from neonatal and mature animals bind E-sdectin, suggesting that prior antigen stimulation and differentiation to a memory lymphocyte are not required for this interaction. Neuraminidase treatment of the γ/δ T cells or addition of ethylenediaminetetraacetic acid (EDTA) to the assay abrogates binding, demonstrating the importance of sialic acid and divalent cations, which is consistent with other E-sdectin-mediated adhesion events. However, previously defined E-selectin carbohydrate ligands, such as sialyl Lewis x on nentrophils and the HECA-452 epitope on human memory lymphocytes, are antigenically different than the carbohydrates on ruminant γ/δ T cells since the mAbs CSLEX and HECA- 452 do not recognize these ceils. Protease treatment of γ/δ T ceils significantly inhibits their binding to E-sdectin; however, previously characterized adhesion glycoproteins, such as L-selectin, CD44, and CD18, are not involved in the adhesive event. An E-sdectin aflinity column purifies a single glycoprotein of 250 kD (280 kD under reducing conditions) from γ/δ T cell detergent lysates. Nenraminidase digestion of the 250-kD product as well as EDTA abolishes bindingto E-sdectin. Finally, E-sdectin expression in vivo appearsto mediate γ/δ T cell accumulation. Stimulation of bovine skin with tumor necrosis factor of induced an increase in E-sdectin expression that was associated with an influx of γ/δ T cells at the same site.