Streptococcal mitogen (SM) is an extracellular product of group A streptococci, which is nonspecifically mitogenic for both B and T lymphocytes. The mitogenic activity of SM is resistant to digestion with trypsin, to heating at 100 degrees C for 5 min and to treatment with dithiothreitol. The proliferative response of lymphocytes from patients with a history of rheumatic fever is similar to that of lymphocytes from healthy donors when stimulated with optimal concentrations of SM, but is significantly reduced when low doses of SM are used. T lymphocytes stimulated with SM acquire la antigens and the ability to stimulate allogeneic and autologous lymphocytes in mixed lymphocyte reactions. An involvement of la antigens in these reactions is indicated by the specific block by monoclonal antibodies. T lymphocytes may acquire la antigens following exposure to an appropriate antigen. If this occurs following a streptococcal infection, these in vitro findings suggest that la bearing T cells may play a role in the immunopathological events which can follow a streptococcal infection. The system described may be a useful in vitro model to analyse the immunopathological events which can follow a streptococcal infection and to develop therapeutic approaches to autoimmune conditions.