We investigated whether immunosuppressive therapy using methylprednisolone (mPSL) with or without cyclosporin A (CsA) could benefit patients with myelodysplastic syndrome (MDS). Eligibility criteria for this study were a clinical diagnosis of MDS with less than 5% blast in peripheral blood, less than 10% blast in bone marrow and advanced cytopenia. Among 73 patients with MDS, 18 eligible and consecutive patients (8 men and 10 women), aged 48 to 87 years (median: 66.5 years) were assigned to receive mPSL pulse therapy (1,000 mg daily for 3 consecutive days, followed by tapering oral prednisolone; n= 12) or mPSL pulse with CsA therapy (4 to 5 mg/kg administered twice daily; n= 6). Six of 18 patients (33.3%; 3 of 10 patients with RA, 2 of 6 patients with RAEB, 1 of 2 patients with CMMoL) responded to immunosuppressive therapy. Four patients responded to mPSL pulse alone, and two patients responded to mPSL pulse with CsA. One of 6 patients with hypocellular bone marrow and 5 of 12 patients with normocellular or hypercellular marrow responded to immunosuppressive therapy. No patient with myelofibrosis responded to the therapy. The duration of response ranged from 4 to 59 months (median: 14 months). Although a significant difference was observed between responders and nonresponders in the survival rate ( P<0.05), no significant difference was found in clinical characteristics at entry between responders and nonresponders. In responders, mean hemoglobin levels were significantly increased ( P<0.01), and the required red cell transfusion dose was significantly reduced ( P<0.01). It is possible that immunosuppressive therapy might be effective for a certain subset of patients with MDS.