The present report critically reviews the rationale, experimental and clinical effectiveness and limits of anti-CD4 monoclonal antibody (mAb) therapy. References are also made to a novel approach involving active immunotherapy and an anti-idiotypic mAb bearing the internal image of human CD4 antigen. Preliminary observations concerning the effects of this treatment in one patient with rheumatoid arthritis and in one patient with systemic lupus erythematosus are reported.