AbstractIt has been hypothesized that the selective recognition of tissue‐specific endothelial cell molecules helps determine thein vivodistribution of lymphoid effector cells by controlling the extravasation of their circulating precursors. Here we report (a) immunofluorescence studies of the cell surface phenotype of human lamina propria lymphocytes (LPL), including staining with monoclonal antibody Hermes‐1, which defines a 90‐kDa lymphocyte surface glycoprotein involved in recognition of high endothelial venules (HEV); and (b) functional analyses of the ability of LPL to bind to HEV in frozen sections of mucosal lymphoid tissues (appendix or Peyer's patch)vs.peripheral lymph nodes. Essentially all LPL bear the Hermes‐1 antigen, over 90% at levels comparable to those of circulating PBL. As a population, LPL display a quantitative preference for adherence to mucosal HEV, binding 0.8–1.5 times as well as PBBL to mucosal HEV, but only 0.1–0.5 times as well to HEV in peripheral lymph nodes. Of particular interest was the behavior of the lymphoblast fraction, which typically constituted 3–7% of LPL. These cells, defined by size, consisted of a mixture of T cells and surface IgA blasts. One hundred percent were Hermes‐1bright, and they bound 4–8 times more efficiently to mucosal HEV than PBL while failing to bind detectably to lymph node HEV. LPL binding to mucosal HEV involves the gp90Hermes, since the monoclonal anti‐gp90 antibody, Hermes‐3, and a polyclonal anti‐gp90 antiserum inhibit the binding of small LPL and of LP blasts. The remarkable efficiency and specificity of binding by LP blasts may reflect retention of homing properties of the blood‐borne precursors of these blasts and is discussed in relation to the capacity of immunoblasts in mesenteric nodes and in thoracic duct lymph to traffic selectively to mucosal lymphoid and extralymphoid sites. The demonstration of organ‐specific endothelial cell recognition by LP lymphoblasts provides considerable support for the concept that selective interactions with endothelium play an important role in directing the distribution of activate