T cells bearing the gamma delta T cell receptor localize largely in epithelial tissues, but are also present at low frequency in organized secondary lymphoid organs. To assess the role of cell surface adhesion molecules in the traffic and tissue localization of gamma delta T cells, we compared the expression of these molecules on both alpha beta and gamma delta T cells in several lymphoid and non-lymphoid organs. In the gut epithelium, gamma delta cells express less LFA-1 (CD11a), Pgp-1 (CD44), and alpha 4 integrin than the corresponding alpha beta cells. In lymph nodes (LN) and Peyer's patches (PP), adhesion molecule expression by gamma delta cells is heterogeneous, with some of the cells having a phenotype similar to that of intraepithelial gamma delta cells and the rest expressing high levels of CD44 and L-selectin (CD62L) but lower beta 7 and alpha M290, a phenotype more like lymph node alpha beta cells. Therefore, the particular set of adhesion molecules expressed by a T cell is dependent, in part, on its anatomic location. Superimposed upon this, however, are differences in expression that are based on the type of T cell; LN and PP gamma delta T cells express less CD44 but much more beta 7, alpha M290 and ICAM-1 (CD54) than alpha beta T cells in the same organ. The differences in adhesion molecules between alpha beta and gamma delta cells are not due simply to differences in their activation status, because these molecules are regulated differently after activation through the T cell receptor (TcR)/CD3 complex. The differential expression of adhesion molecules on cells bearing a particular TcR V region suggests that distinct adhesion phenotypes may arise from prior contact with specific antigen and resultant cell activation in vivo. Lastly, the presence of high level expression of alpha 4 beta 7 and alpha M290 on L-selectinlo gamma delta cells in lymph nodes suggests that these gamma delta cells may be uniquely capable of migrating to the gut. The differences in adhesion molecule expression and regulation between gamma delta and alpha beta T cells could explain, in part, the distinct homing and tissue localization of these T cell subsets in vivo.