Objective. To determine whether modulation of activated T cells occurs in patients with rheumatoid arthritis (RA) after immunization with T cell receptor (TCR) Vβ17 peptides, a phase I trial was initiated to investigate the safety and feasibility of TCR peptide immunization as a therapeutic approach in RA. Methods. 15 patients with moderate to severe RA were given an intramuscular injection of one of 4 doses (10, 30, 100, and 300 μg) of the VβI7 peptide vaccination, followed by a booster injection of the same dose of vaccine 3 weeks later. Patients were followed for 48 weeks. Results. The product was well tolerated and no serious adverse events attributable to the vaccine were observed. This was an uncontrolled phase I trial, however; decreases in patient joint scores were observed at all followup visits starting at 4 weeks after primary immunization. Activated Vβ17 T cells (IL-2R+) in peripheral blood were decreased (≤ 20%) in 3/5 patients in the 100 μg group after initial measurement at Week 2 and 3/4 patients in the 300 μg group 3 weeks after immunization. Lymphocyte proliferation in response to the Vβ17 peptide was detected at 6 weeks or later after primary inoculation in 6/15 patients (40%) immunized. Conclusion. Further controlled studies are required to assess the biologic and clinical efficacy of this treatment approach.