Lymphokine-activated killer (LAK) cells are able to colonize sites of tumor lesions in mouse and man. The molecular mechanisms of homing in on tumors are largely unknown. However, before LAK cells can reach the tumor, they must adhere to the vascular endothelial within the lesion and then extravasate. We developed a novel mAb, EA-3, which recognizes the murine homologue of the human adhesion molecule CD31. It is present on a subpopulation of murine LAK cells and all endothelial cells. CD31 was also involved in the adhesion of LAK cells to endothelium. Since CD31 can initiate integrin activation by inside-out signaling after binding to its ligand, EA-3 was used to minimic this in adhesion assays. It induces modifications in the beta 2 integrin LFA-1, leading to increased binding capacities of the cells to endothelium. In contrast, beta 1 integrins and RGD-binding integrins were not affected. These results suggest that expression of CD31 might confer adhesive advantages for LAK cells prone to tumor infiltration.