This pilot study will seek to investigate the use of rituximab in patients with Wegener's granulomatosis who have experienced disease relapse through standard therapies. Rituximab is a chimeric monoclonal antibody directed against CD20, which induces B cell death and results in rapid and sustained depletion of circulating and tissue-based B cells. The objectives of this protocol will be to establish the safety of rituximab in Wegener's granulomatosis, to examine the ability of rituximab to reduce the level of circulating antineutrophil cytoplasmic antibodies (ANCA), and to preliminarily explore whether rituximab is able to prevent disease relapse. This prospective standardized open label trial will enroll 10 patients who have a well-documented history of disease relapse while receiving immunosuppressive therapy given according to published regimens and who are ANCA positive after remission induction. Patients will be enrolled once they have achieved remission from a recent relapse and are receiving either methotrexate or azathioprine for remission maintenance. All patients will receive rituximab 375 mg/M(2) once a week for 4 weeks. During and following the rituximab treatment period, patients will remain on their remission maintenance agent of methotrexate or azathioprine. Patients who are enrolled while on prednisone will continue to taper the dosage to discontinuation as medically permitted. Following the 4 weekly infusions of rituximab, patients will be followed prospectively for evidence of effective B cell depletion, features of drug toxicity, level of circulating ANCA, and clinical disease status. Patients whose ANCA levels become undetectable following the infusion of rituximab may be retreated with a second 4 week course of rituximab should their ANCA titer become positive (greater than or equal to 1:40) and there has been a return of B cells in the peripheral blood. Methotrexate or azathioprine will be continued for two years past remission, after which time, this will be tapered and discontinued. Patients will continue to be monitored for two years off all immunosuppressive therapy or if a disease relapse should occur, for a minimum of 12 months after the last rituximab infusion.