The reticulum cell sarcomas (RCS) of SJL/J mice are of particular interest since they readily induce the proliferation of syngeneic T lymphocytes. Previous cellular studies examined the antigens on the RCS which stimulated this response and suggest that the tumor expressed alogeneic I-region-associated (la) antigens normally associated with the E.alpha.:E.beta. molecular complex (S. M. Wilbur and B. J. Bonavida, 1981). These particular la glycoproteins are not expressed on normal SJL/J cells due to a defect in the E.alpha. polypeptide synthetic pathway. The E.beta. subunit is synthesized normally by these animals but remains intracellular. The SJL/J-derived RCS may circumvent this defect in E.alpha. subunit biosynthesis. The aberrant synthesis of this polypeptide is thought to allow membrane presentation of an intact pseudoallogeneic la glycoprotein which utilized the normally dormant E.beta.s polypeptide. Two monoclonal antibodies directed against the la.7 specificity of the E.alpha. chain (13/18, 14-4-4S) were used to examine more directly the expression of this polypeptide on the tumor. Neither antibody was effective against the RCS in a direct complement-mediated cytolysis assay. The tumor specifically adsorbed lytic activity of both the monoclonal antibodies. Both a cold-cell competition assay and indirect immunofluorescence corroborated the data and indicated that the RCS does express detectable levels of the la.7 antigen. Normal spleen cells and lipopolysaccharide B-derived blasts from SJL/J mice in all experiments were devoid of any specific reactivity with these monoclonal antibodies. Continued in vivo passage of transplantable RCS caused down-modulation of the la.7 specificities on these tumors. Newer RCS transplantable lines expressed demonstrable levels of this alloantigen in both cellular and serological assays. The observed down-modulation could explain the difficulties encountered in defining this specificity on long-term transplantable RCS. The serological study corroborates early cell-binding data. An la.7 antigen is expressed on the RCS, yet this specificity could not be detected on nomral SJL/J cells.