We address the relationship between reactive hemophagocytic syndrome (RHS), systemic lupus erythematosus (SLE) activity, and treatment in 4 female patients with SLE. Febrile pancytopenia was related to cytologically proven RHS in all patients. Followup was 45+/-7 months from RHS onset. No causal infection could be identified. Outcome could be classified as: (1) RHS onset during a SLE flare and complete efficacy of high dose steroids; (2) death despite therapy for concomitant severe RHS and active SLE; (3) severe RHS in inactive SLE under immunosuppressants, with remission after steroid tapering and cyclophosphamide withdrawal. Three patients were treated with intravenous IgG. We conclude that (1) when SLE is active, RHS should be considered a specific manifestation and treated with steroids; (2) RHS occurring in otherwise inactive SLE might be related to iatrogenic immunosuppression; (3) intravenous IgG treatment might be indicated in both situations.