Therapy of systemic lupus erythematosus (SLE) with major organ involvement consists of aggressive immunosuppression with glucocorticoids and cytotoxic agents. When remission is achieved, maintenance therapy is begun to reduce the risk of relapse while minimizing toxicity. Remission with standard therapy is, however, not always achieved. We discribe a women with SLE and microangiopathic haemolytic anaemia and thrombocytopenia, pneumonitis and nephritis refractory to high-dose steroids, pulse cyclophosphamide, plasmapheresis and intravenous immunoglobulins. The anti-CD20 monoclonal antibody rituximab was administered, resulting in major clinical and biochemical improvement. Therapy-resistant SLE generally has an ominous prognosis. A few anecdotal reports and small open studies describe beneficial effects of rituximab in these cases. Rituximab may be a promising new approach to improve the dismal outcome of therapy-resistant SLE.