We have cloned a previously undescribed adhesion molecule, VCAM-1, which is induced by cytokines on human endothelial cells and binds lymphocytes. Using a novel method requiring neither monoclonal antibodies nor purified protein, VCAM-l-expressing clones were selected by adhesion to human lymphoid cell lines. VCAM-1 mRNA is present in endothellal cells at 2 hr after treatment with IL-1 or TNF-a and is maintained for at least 72 hr; leukocyte binding activity parallels mRNA induction. Cells transfected with VCAM-1 bind the human leukemia lines Jurkat, Ramos, RJI, HWO, and THPl, but not peripheral blood neutrophils. VCAM-1, which belongs to the immunoglobulin gene superfamily, may be central to recruitment of mononuclear leukocytes into inflammatory sites in vivo.