We recently showed that CD48 is the major counter-receptor for CD2 in the murine system. To examine whether sgp-60, which has been proposed as the murine homologue of human LFA-3, is another ligand for mouse CD2, we performed the characterization of sgp-60 by using mouse CD2-human IgG chimeric protein (mCD2Rg) and anti-mouse monoclonal antibodies (mAb). Anti-sgp-60 mAb 5-8A10, as well as anti-mouse CD48 mAb HM48-1 completely inhibited the binding of mCD2Rg at the ligand site. 5-8A10 immunoprecipitated the same molecule as that recognized by HM48-1 and reacted with mouse CD48 cDNA-transfected chinese hamster ovary cells, indicating that sgp-60, recognized by 5-8A10, is identical to mouse CD48. The epitope recognized by 5-8A10 was different from that recognized by HM48-1 and OX78, suggesting that the different T cell activating property of these anti-mouse CD48 mAb depends on the epitopes they recognize. The identification of sgp-60 as CD48 further suggests a role of CD48 in regulating T cell activation.