OBJECTIVE: To describe the safety and efficacy of rituximab in the treatment of childhood-onset systemic lupus erythematosus (SLE). STUDY DESIGN: We conducted a French multicenter retrospective study of childhood-onset SLE treated with rituximab. RESULTS: Eleven girls with severe SLE, including 8 girls with class IV or V lupus nephritis, 2 girls with severe autoimmune cytopenia, and 1 girl with antiprothrombin antibody with severe hemorrhage, were treated with rituximab. The mean age at onset of rituximab treatment was 13.9 years. Patients received 2 to 12 intravenous infusions of rituximab (350-450 mg/m2/infusion), with corticosteroids. Six patients also received different standard immunosuppressive agents, including Cyclophosphamide (2 patients). Remission was achieved in 6 of 8 patients with lupus nephritis and in the 2 patients with autoimmune cytopenia. Steroid therapy was tapered in 5 patients who responded to treatment, and low-dose prednisone treatment was maintained in 1 patient. The mean follow-up period was 13.2 months (range, 6-26 months), and remission lasted in all who patients who responded to treatment, except 1 patient who was successfully retreated with a second course of rituximab. Anti-double-stranded DNA antibody levels decreased in 6 of 11 patients, and anticardiolipin antibody levels decreased in 3 of 4 patients. Severe adverse events developed in 5 patients. Effective depletion of peripheral blood B cells was observed in 7 of 8 patients who were examined, and this paralleled the remission. CONCLUSION: Rituximab may be an effective co-therapy; however, further investigations are required because severe adverse events occurred in 45% of the patients in this study.