BACKGROUND: Many patients with various autoimmune diseases fail to respond to conventional immunosuppressive therapy and develop irreversible organ damage. In some cases the complications might be fatal. Furthermore, prolonged immunosuppression with cyclophosphamide or corticosteroids often leads to long-term side effects, cumulative organ damage, and development of secondary malignancies. THERAPY: Thus, short-term, high-dose immunosuppressive therapy with autologous stem cell transplantation might be an alternative for otherwise refractory patients. This concept has been used mainly in patients with scleroderma, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. PATIENTS: Patients with primary systemic vasculitis (PSV) seem to be suitable candidates for high-dose chemotherapy (HDCT). Although complete, long-term remissions are possible with standard immunosuppressive therapy, there is a subgroup of patients who cannot be cured by standard therapy. They need long-term immunosuppression and eventually die due to progression of the disease or cumulative therapy-related toxicity. In large series, the 5-year mortality rate was > 20%. The severity of vasculitis rather than the distinction between subgroups should determine whether HDCT might be a life-saving treatment. RESULTS AND CONCLUSION: Careful patient selection with the help of scoring systems and determination of the optimal time in the course of disease are now the major goals in the approach to HDCT. First reports as well as our own single-center experience in HDCT with a limited number of patients with severe PSV have shown that long-term remissions are possible even in patients refractory to conventional immunosuppression.