Mycophenolate mofetil (MMF) is an effective immunosuppressive agent in renal transplantation, and preliminary studies suggest that it may also be effective in the treatment of lupus nephritis. This study investigated the efficacy and safety of MMF therapy in patients with refractory primary nephrotic syndrome in a prospective multicentre clinical observation. Nineteen refractory nephrotic patients with minimal change disease or mesangial proliferative glomerulonephritis were enrolled in this study. Combined MMF and prednisone therapy was used for 6 months with an initial MMF dose of 1.0-2.0 g/day and a prednisone dose of 20-60 mg/day; both drugs were tapered gradually. It was found that all patients achieved clinical remission and 11 of 19 responded within 4 weeks, and 12 of 19 patients entered complete clinical remission. The prednisone dose in those patients who were previously steroid dependent could be successfully tapered. During follow up, three patients experienced transient increasing of proteinuria associated with infections and recovered without an adjustment of therapy. One patient was withdrawn from the study because of a fall in haemoglobin levels; other adverse effects did not necessitate withdrawal. Follow-up renal biopsies in two patients found no alteration in renal pathology. Mycophenolate mofetil is an effective and well-tolerated immunosuppressive agent for patients with refractory nephrotic syndrome.