Background and method: This clinical experience involved the treatment of resistant systemic lupus erythematosus (SLE) patients with CD20 monoclonal antibody. Five patients failed conventional therapy, two developed complications and one needed rituximab as an emergency measure. Four patients had lupus nephritis, three had autoimmune hemolytic anemia, two had immune thrombocytopenia and one had lupoid hepatitis. The patients were aged 14-49 years, (mean 28.63). Three were Malays, two Chinese, two Indian and one Turkish; six were females. Mean disease duration was 63.25 months and mean total rituximab dose received was 2812.50 mL. Results: Hemoglobin levels improved from 9.3 ± 5.7 to 13.1 ± 8.6 g/dL for two SLE patients with autoimmune hemolytic anemia after 34 weeks (P = 0.180). Platelet counts improved from 25 ± 17 to 198 ± 97 × 10 9/high powered field from 0 to 10 weeks for three SLE patients with immune thrombocytopenia (P = 0.109). In the lupus nephritis patients on rituximab, serum albumin improved from 24.5 ± 23.2 to 37.5 ± 31.8 mmol/L (n = 3) from week 0 to week 17 (P = 0.100). Urine protein creatinine ratio improved from 0.55 ± 0.23 to 0.08 ± 0.03 g/mmol creatinine (P = 0.068) from week 0 to week 13. C3 and C4 improved from 90.8 ± 36.5 to 120.7 ± 37.9 (P = 0.07) and 21.6 ± 10.1-27.3 ± 16.2 mg/dL (P = 0.27), respectively, and Systemic Lupus Erythematosus Activity Disease Index was reduced from 17.9 ± 11.2 to 6.3 ± 6.8 (P = 0.375) after 8 weeks. Two patients developed drug reactions to rituximab. Conclusion: All of the patients responded to rituximab on top of their conventional therapy. © 2007 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.