Rheumatoid arthritis (RA) is a chronic multisystemic disease affecting mainly the joints and characterised by a poor prognosis. In a four month open study we evaluated the efficacy and tolerability of a combination therapy in 14 patients with active and refractory RA (non responsive to MTX or CsA monotherapy). After three pulses of methyl-prednisolone (125 mg/die i.v. for 3 days), at day the 4 patients received methotrexate (MTX 15/mg/week p.os) and cyclosporine (CsA 3 mg/kg/day p.os). At the end of treatment period, patients had a statistically significant improvement in the tender-joint count (Ritchie Index) in the swollen-joint count and in the pain as recorded on a 100-mm visual-analogue scale. Following the criteria of the American College of Rheumatology for response to treatment in RA, 6 patients (60%) met these criteria, whereas 2 had a worsening. We could not detect any clear difference in serological parameters (ESR, CRP and Hb levels) between the beginning and the end of the therapy. A significant difference in the score of edema/joint effusion was documented at the RM analysis. Side-effects were not substantially increased as compared to MTX or CsA in single therapy. Combination therapy with CsA and MTX seems to be a safe and effective treatment for patients with active and refractory RA.