In this prospective, non-comparative case series, four patients with severe and highly active adult-onset Still's disease (AOSD), refractory to high doses of corticosteroids (which had been combined with methotrexate in three of them) and methotrexate were treated with infliximab (initial dose 3-5 mg/kg, continuing at intervals depending on the patient's individual disease activity). Resolution of their symptoms, which was evident within few days after the first infusion, and a parallel rapid improvement of the acute inflammatory response indices were observed in all. Concomitant corticosteroid treatment was reduced after the first courses of treatment with infliximab, which was well tolerated, and complete disease remission was sustained during a 5-18-month follow-up period. Although further studies to confirm long-term efficacy and safety in larger numbers of patients are needed, we suggest that administration of infliximab with observation for objective improvement is the treatment of choice in cases of AOSD refractory to conventional treatment.