Recently, interest has grown in the potential benefit of vaccination approaches in humans with rheumatoid arthritis. Approaches evaluated include the use of T cell receptor peptide vaccines, autologous T cells, major histocompatibility complex (MHC) peptides, allogeneic mononuclear cells and oral collagen. The use of T cell receptor peptide vaccination in rheumatoid arthritis has been limited to dose-finding and pharmacokinetic studies with Vbeta14 and Vbeta17 peptides. The results of an ongoing placebo-controlled clinical trial with a combination of Vbeta3, Vbeta14 and Vbeta17 peptides will be of interest. Since the pathogenic T cells in rheumatoid arthritis are not known, the use of mixed T cell populations for attenuated autologous T cell vaccination may be necessary. This approach has been evaluated in a small number of patients. Significant clinical or adverse effects were not observed. The appropriate dose, route of administration and method of attenuation of autologous T cells remains to be more clearly defined. In addition, any immunisation approach that targets T cells that are not pathogenic has the potential of immunising against beneficial T cell clones. Rheumatoid arthritis is associated with certain MHC class II alleles (e.g. HLA-DR1 and DR4). Rheumatoid arthritis frequently remits during pregnancy, although the mechanisms associated with this are not clear. Based on this observation, several therapeutic approaches have been evaluated in rheumatoid arthritis. These include placenta-eluted gamma globulins (which contain antibodies to HLA-DR antigens), DR4/DR1 peptide vaccines and allogeneic mononuclear cell vaccination. In uncontrolled trials, each of these approaches has been shown to have no adverse effects and encouraging clinical benefits have been observed, although double-blind placebo-controlled studies will be needed to assess these approaches. Encouraging clinical results have been reported to date with oral administration of type II collagen as a therapy for rheumatoid arthritis, and large multicentre controlled trials are currently under way.