In recent years, there has been a dramatic rise in the number of trials using monoclonal antibodies, especially those directed against the CD4 molecule, in the treatment of RA. Thus far, the numbers of patients treated in the individual studies have generally been small, and the study designs sometimes not comparable. All of the trials have so far been conducted in a non-blinded, uncontrolled fashion. The patient populations usually represented the far end spectrum of individuals who had failed all other conventional and/or experimental approaches. Clearly, therefore, larger controlled double blind studies in patients with less advanced stages of RA are needed. Moreover, with the exception of one or two reagents (MAX.16H5 and possibly B-F5) apparently routine laboratory parameters determining disease activity usually remain unaltered upon anti-T cell therapy. In addition, in some individuals there has been no clinical improvement despite sometimes severe CD4 cell depletion. Nevertheless, the available data indicate that this form of treatment leads to significant immunomodulation with marked changes in clinical and laboratory parameters and may therefore be a promising approach to the treatment of RA.