Monoclonal antibodies against the mouse sarcoma FS9 were prepared. Antibodies recognizing a 37,000 dalton glycoprotein on FS9 tumor cells inhibit invasion by FS9 sarcoma cells of chicken heart fibroblasts in vitro as assessed by Abercrombie's confronted explant assay. Antibodies to other membrane proteins of FS9 tumor cells failed to inhibit invasiveness of FS9 sarcoma cells. The 37,000 dalton glycoprotein, which is neither a histocompatibility antigen nor a gp37 glycoprotein of Rous sarcoma virus nor the MEP described by Gottesman, is present on the surface and in the cytoplasm of FS9 sarcoma cells. The plasma membrane of the non-invasive mouse cell line L929 contains only low concentrations of the 37,000 dalton antigen. Hence, a relationship apparently exists between the increased concentration of this protein on the surface of FS9 cells and their invasiveness.