Kidney transplant glomerulopathy (TG) has a poor outcome as there are no known effective therapies. Therefore, we investigated whether rituximab therapy (RTx) could halt progression of established TG. Fourteen kidney-transplant patients (nine of whom were men), with median age of 54 (range: 30-74) years, of whom seven had biologic markers for HCV infection, underwent a kidney biopsy (KB) at 118 months post-transplant because of impaired allograft function, associated with albuminuria (95-13430 mg/day), within nephrotic-range albuminuria in seven patients. KBs showed no evidence of acute cellular rejection but showed TG. Donor-specific anti-HLA antibodies were present in six cases. When diagnosis of TG was made, patients were placed on rituximab therapy (RTx) (2-4 injections of 375 mg/m2 week), and other concurrent immunosuppression treatments were not modified. By last follow up post-RTx (30 months), seven (50%) patients had lost their kidney within 6-26 months and the other seven had stable creatinine (182 vs. 161 micromol/l; NS), and albuminuria had decreased from 2660 to 500 mg/day (P = 0.03). There was prolonged B-cell lymphopenia (from 71 to 0/mm3) whereas immunoglobulin G, A, M levels remained stable, and four patients (28.5%) experienced severe infectious complications. We conclude that long-term RTx in kidney-transplant patients with TG is associated with allograft function/stabilization in 50% of cases.