Methods. The clinical charts of 41 consecutive Italian AOSD patients were evaluated with special attention to liver involvement. Serum levels of IL-18 were measured in 21 patients. Finally, the case of a 33-year-old woman with hepatitis where a liver biopsy was obtained and sections stained with antibodies against IL-18 and CD68 is described in detail. Results. Of the 41 AOSD patients, 32 and 39% displayed increased AST level or ALT level, respectively, generally normalizing with steroid treatment, while 41% had evidence of hepatosplenomegaly. Circulating IL-18 levels were significantly higher in those with active disease compared with 85 controls. A correlation was observed between IL-18 serum level and disease activity, serum ferritin level and neutrophil count. IL-18 concentration was markedly increased in the patient with active hepatitis. Intense IL-18 expression was detected within the liver parenchyma and double staining with IL-18 and CD68 clearly showed colocalization of the cytokine with the macrophage marker. Conclusion. Macrophage-derived IL-18 might play a central role in the pathogenesis of AOSD. IL-18 serum level is higher in patients with active AOSD and its local, rather than systemic, expression may be responsible for tissue damage in some target organs, such as liver.