The human CD2 antigen is a T lymphocyte cell surface glycoprotein that has been implicated in both T lymphocyte adhesion and activation. The requirement for a T lymphocyte-specific factor(s) in the mechanism of signal transduction initiated via the CD2 antigen has been explored using murine L cells transfectants that stably express the human CD2 antigen at the cell surface. Such transfectants express the three CD2 epitopes previously defined on human T lymphocytes. However, combinations of CD2 monoclonal antibodies, that stimulated an increase in the cytoplasmic calcium concentration of the human T cell line Jurkat, failed to induce a similar signal in the transfectants. These results indicate that the transfected CD2 antigen cannot alone transduce intracellular signals in response to stimulatory combinations of CD2 monoclonal antibodies, and suggest that the functional CD2 antigen expressed on human T lymphocytes requires the association of another, as yet undefined factor(s).