TISSUE-SPECIFIC homing of lymphocytes is regulated by interac-tions with the endothelium of specialized venules, such as the high endothelial venules (HEY) in lymph nodes and mucosal Ivmphoid tissues^1–3. The mucosal vascular addressin, a 58–66K glycoprotein adhesion receptor for lymphocytes, is selectively expressed on HEV of mucosal lymphoid organ and on lamina propria venules and helps direct lymphocyte traffic to these mucosal tissues^4,5. We now report the isolation of a complementary DNA that, on transfection into COS cells, encodes immunoreactive addressin that specifically binds the mucosal HEV-binding T-cell lymphoma TK1. The predic-ted amino-acid sequence defines the mucosal addressin as a novel immunoglobulin family member, MAdCAM-1, with two amino-terminal domains that display strong homology to previously described vascular adhesion receptors for leukocytes, ICAM-1 (ref. 6) and VCAM-1 (ref. 7). The membrane proximal domain is homologous to the third domain (Cα2) of another mucosa-associ-ated immunoglobulin family member, IgA1 (refs 8,9). In addition to the immunoglobulin domains, there is a erine/threonine-rich region which may serve as a backbone to present carbohydrate ligands to lymphocytes. MAdCAM-1 is thus a complex multi-domain receptor displaying several structural motifs that may participate in lymphocyte homing interactions.