The renal diseases associated with monoclonal immunoglobulin deposits constitute a diverse range of clinical and pathological entities. Renal prognosis is variable, and there currently are no standard treatment regimens. We describe the effect of rituximab treatment on 3 patients with renal insufficiency and proteinuria with monoclonal immunoglobulin deposits associated with glomerulonephritis on renal biopsy. Two patients with hypertension and chronic lymphocytic leukemia had a membranoproliferative glomerulonephritis pattern on kidney biopsy associated with monoclonal immunoglobulin G deposits. Both patients experienced partial remission of their disease and 1 patient was able to come off hemodialysis therapy after treatment with 7 and 11 biweekly doses of rituximab, 375 mg/m(2), in addition to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker. Both patients subsequently experienced relapse of their hematologic and renal diseases and eventually progressed to end-stage renal disease and death. A third patient had diffuse proliferative glomerulonephritis with immunoglobulin G lambda deposits on renal biopsy. She was treated with an angiotensin receptor blocker and two 1,000-mg infusions of rituximab separated by 2 weeks, with sustained partial remission at 18 months' follow-up. Rituximab therapy, in addition to corticosteroids and angiotensin blockade, may improve the clinical course of patients with renal diseases associated with dysproteinemias, delaying the onset of end-stage renal failure or other adverse outcomes. Additional clinical studies should be planned.