Based on the experience that T helper lymphocytes play an important part in the initiation and maintenance of various autoimmune diseases and also in graft rejection, novel therapeutic approaches have been developed and are under investigation. They are aimed at selective inhibition of T cells whose activation is unwanted. Useful tools for this purpose are monoclonal antibodies to cell surface molecules which are restricted to certain cell populations. In this review the concept of treatment with antibodies to CD4-a surface molecule characteristic of T helper lymphocytes-is discussed. Encouraged by experimental experiences obtained during the past years, a series of case reports were published and clinical pilot studies have been performed, the preliminary results of which are now becoming available. Anti-CD4 therapy appears to be a promising approach. Short-lasting effects can be separated from long-lived effects. The latter are not easy to explain, although hypotheses have been developed still requiring more detailed experimental confirmation.