There is no consensus regarding the modality of therapy for idiopathic membranous nephropathy (IMN), especially for patients who did not react to treatment with cytotoxic drugs. This study followed prospectively for 3-year IMN patients who did not react to Ponticelli protocol comparing effects of 2-year course of cyclosporine (CsA) with azathioprine (Aza) treatment both with small doses of prednisolone. Twenty-three patients were randomly assigned to receive either cyclosporine at 3mg/kg per day (10 patients) or azathioprine at 1.5 to 2mg/kg (13 patients). Both groups were comparable regarding age, sex and renal function, except for proteinuria, which was significantly greater in CsA group (P=0.003). Similar rate of remission of nephrotic syndrome (NS) have been noted at the end of treatment (80% CsA versus 93% Aza). During last year, follow-up relapses of NS were more frequent in Aza group (5 versus 1). A fall in proteinuria was recorded in both groups during treatment, but it rose significantly in Aza group (1.5g/day versus 3.1g/day, P=0.04) and remained unchanged in CsA group (3.9g/day versus 4.1g/day) after treatment cessation. Renal function deteriorated in Aza group (sCr 120.5 versus 269.8μmol/L; P<0.01) and was stable in CsA group. In conclusion, CsA and steroids may be a very important option in the management of high-risk IMN patients. Long-term treatment is necessary for achievement of full therapeutic effect. Treatment with Aza did not have long-term benefits particularly regarding renal function preservation.