The efficacy of low-dose cyclosporin-A (CyA) has been clearly demonstrated for rheumatoid arthritis. However, the long-term benefit-risk ratio remains to be investigated in patients with refractory RA. Thirty one patients were included in a prospective open study (24 females, seven males, mean age = 55 years). The mean duration of RA was 11 years and refractory RA was defined by the need of corticosteroid treatment in 26 patients and the previous failure of at least five second line drugs including methotrexate in 27 patients. Initial dosage of CyA was 3 mg/kg/d and could be progressively increased up to 5 mg/kg/d. The mean duration of the study was one year (3-39 months). At 3 months, clinically relevant improvement occurred in 22 patients (71%). Seven were withdrawn due to inefficacy. The main side-effects were hypertension (22 cases) and nephrotoxicity (18 cases) requiring the withdrawal from the study, respectively in one case and in four cases. Raised serum creatinine level had required reduction of the dosage with loss of efficacy in four cases. CyA appears to be an effective therapy for severe treatment refractory RA. Despite a high incidence of side-effects, the efficacy and the monthly management of the patients lead to a good benefit/risk ratio with a percentage of continuation of treatment of 42% at one year.