We studied the adhesion properties of peripheral blood leukemic cells from 10 patients with adult T-cell leukemia (ATL) to endothelial cells to better understand the mechanism of leukemic cell infiltration. ATL cells expressed lymphocyte function-associated antigen-1 (LFA-1), but the expression of very late antigen-4 (VLA-4) and sialyl-Lewisx (SLex) was variable. They did not express sialyl-Lewisa (SLea). Cell adhesion assays, which were performed in nine patients, showed marked adhesion of ATL cells to interleukin [IL]-1-activated human umbilical vein endothelial cells (HUVEC). A monoclonal antibody (MoAb) against E-selectin consistently inhibited ATL cell adhesion, and an MoAb against vascular cell adhesion molecule-1 (VCAM-1) or an MoAb against VLA-4 sometimes diminished it. In contrast, an MoAb against LFA-1 had a minor effect on freshly isolated ATL cell adhesion to HUVEC. The percentage of SLex+ cells in the cell population adherent to IL-1-activated HUVEC was slightly higher than that in unseparated cells. These results, together with the detection of E-selectin expression on the endothelium at ATL skin lesions, indicate that E-selectin-mediated adhesion is the major pathway for the adherence of ATL cells to endothelial cells. In addition, the ligand for E-selectin on ATL cells appears to differ from that on neutrophils.