The emergence of monoclonal antibody technology has fostered new therapeutic strategies for people with autoimmune diseases. One of the most promising of these strategies involves the use of CD4 monoclonal antibodies, which are effective in animal models for systemic lupus erythematosus, diabetes mellitus, rheumatoid arthritis, myasthenia gravis, and multiple sclerosis. The appeal of CD4 antibodies is enhanced by several factors: (1) their effectiveness does not depend on depletion of target cells; (2) they may block the host immune response to therapy, and (3) they have been well-tolerated in preliminary human trials. The principal obstacle to the use of CD4 monoclonal antibodies stems from their adverse effects on normal immune function.