Systemic onset juvenile rheumatoid arthritis (SOJRA) is a multisystem disease characterized by high fever, rash, arthritis, serositis, splenomegaly, and laboratory evidence of systemic inflammation. Anticytokine therapies show promise in the treatment of chronic arthritides in children. We describe the use of the recombinant interleukin 1 receptor antagonist anakinra in 2 patients with therapy resistant SOJRA. Both patients experienced immediate and sustained resolution of symptoms and laboratory markers of inflammation, in one case after years of treatment with other immunosuppressive therapies.