The murine CD18 monoclonal antibody (mAb) M18/2 was reported to inhibit lymphoma metastasis [Zahalka, M. A. et al. (1993) J. Immunol. 150, 4466]. To identify the pathways potentially blocked, we studied the effects of M18/2 compared with two new mAb against murine CD18, GAME‐46, and ‐245. Whereas the GAME mAb blocked most Mac‐l‐mediated interactions, M18/2 had no effect, or even stimulated. The same was true for adhesion of LFA‐1 to ICAM‐1. To test effects on interactions with different ICAMs, we used L cells transfected with human IGAM‐1, ‐2, and ‐3. As previously described, mouse LFA‐1 does not bind to human ICAM‐1 but we show here that mouse LFA‐1 does bind to human ICAM‐2 and ‐3. Again, the GAME mAb blocked completely, but M18/2 did not. These results indicate that the LFA‐1 binding sites for ICAM‐1 and ICAM‐2 and‐3, although in close vicinity, are distinct. Furthermore, effects of M18/2 on metastasis cannot be ascribed to blocking of any known β₂‐integrin activity. J. Leukoc. Biol. 60: 758–765; 1996.