T lymphocyte activation can be triggered through multiple distinct, but functionally related, pathways. Murine monoclonal antibodies (mAbs) have been used to characterize the surface components of several of these pathways, as well as structures whose function is not yet known. One such cell surface structure is the heterodimeric 4F2 antigen, which is expressed on activated and proliferating cells. Two new mAbs that recognize the heavy chain of the 4F2 antigen have been produced in our laboratory. One antibody, UM7F8, is comitogenic with soluble anti-CD2 and immobilized (but not soluble) anti-CD3 mAbs. The second antibody, termed UM2G12, appears to recognize a cryptic epitope on the 4F2 heavy chain and is not comitogenic for T cells. In view of the functional effects seen with UM7F8, and the highly regulated expression of the 4F2 antigen, it seems likely that 4F2 has a specific role in T cell development and activation.