Significantly more patients who received 2 500-mg or 2 1,000-mg infusions of rituximab met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 24 (55% and 54%, respectively) compared with placebo (28%; P < ). ACR50 responses were achieved by 33%, 34%, and 13% of patients, respectively (P < ), and ACR70 responses were achieved by 13%, 20%, and 5% of patients (P < ). Changes in the Disease Activity Score in 28 joints (-, -, -; P < ) and moderate to good responses on the European League Against Rheumatism criteria (P < ) reflected the ACR criteria responses. Glucocorticoids did not contribute significantly to the primary efficacy end point, ACR20 response at 24 weeks. Intravenous glucocorticoid premedication reduced the frequency and intensity of first infusion-associated events; oral glucocorticoids conferred no additional safety benefit. Rituximab was well tolerated; the type and severity of infections was similar to those for placebo.