Lymphocyte-high endothelial venule (HEV) cell interaction that is mediated by specific receptors is fundamentally important during normal and malignant lymphocyte traffic. Putative human lymphocyte homing receptors to peripheral lymph node, mucosal (Peyer's patch, appendix) and inflamed joint tissue (synovium) HEV appear to be functionally distinct, but structurally closely related 90 kDa glycoproteins that are highly conserved during evolution. These receptors regulate lymphocyte traffic in an organ-specific manner throughout the body, thus determining the characteristics of local immune responses and possibly also the patterns of dissemination of lymphoid malignancies.