The carbohydrate antigen, sialyl Le^x, is known to be a ligand for the cell adhesion molecule called ELAM-1 (E-selectin, endothelial cell leukocyte adhesion molecule-1), which is present on cytokine-activated human endothelial cells. Recently, we reported that another carbohydrate antigen, sialyl Le^a, can also serve as a ligand for ELAM-1 (A. Takada, K. Ohmori, N. Takahashi, K. Tsuyuoka, K. Yago, K. Zenita, A. Hasegawa, and R. Kannagi, Biochem. Biophys. Res. Commun., 179: 713–719, 1991). Both sialyl Le^x and sialyl Le^a are expressed in many human malignant cells. In order to assess the contribution of these carbohydrate antigens to the adhesion of human malignant cells to vascular endothelium, we selected a panel of 12 cultured human epithelial cancer cell lines and a panel of 12 human leukemia cell lines which express sialyl Le^x and/or sialyl Le^a antigens. All 12 epithelial cancer cell lines exhibited a clearly ELAM-1 -dependent adhesion to cytokine-activated human umbilical vein endothelial cells, while only 3 of the 12 leukemia cell lines exhibited significant participation of ELAM-1 in the adhesion. With regard to epithelial cancer cells, the adhesion of 6 cancer cell lines, mostly of colon and pancreas origin, was dependent almost exclusively on sialyl Le^a. A significant contribution of the sialyl Le^x antigen was noted in the adhesion of the other 6 cell lines, including cancers of lung and liver origin. These results imply that the sialyl Le^a/ELAM-1 adhesion system, as well as the sialyl Le^x/ELAM-1 adhesion system, plays an important role in the adhesion of human cancer cells to human umbilical vein endothelial cells. With regard to leukemia cells, on the other hand, adhesion of the 3 leukemia cell lines that showed ELAM-1-dependent adhesion was mediated by the sialyl Le^x antigen, and none of these leukemia cell lines expressed sialyl Le^a or exhibited sialyl Le^a-dependent adhesion.