 Membranous glomerulopathy MN is still the most common glomerular disease associated with nephrotic proteinuria NS. Up to 40 of patients reach end stage renal failure ESRD, making MN the 2nd or 3rd most common cause of ESRD caused by a primary glomerulopathy. Current treatment options include corticosteroids, alkylating agents, and cyclosporin, but their use is controversial and the associated adverse effects and high cost temper their usage. Experimental data in MN suggests that B cell activation results in immunoglobulin deposition along the glomerular basement membrane causing injury to the membrane and subsequent proteinuria. Drugs that non-selectively inhibit B cells and, these pathogenic antibodies, are closely associated with improved outcomes. Based on the rationale that selective depletion of B cells in humans would prevent the production of ?nephrotoxic? immunoglobulins and subsequent renal injury we recently treated 15 patients with MN with rituximab 1g i.v. twice day 1 and day 15. Baseline proteinuria of 13.05.5g24h decreased to 9.17g, 9.78g and 6.56 g24h at 3, 6, and 9 months, respectively mean SD. Analysis of the pharmacokinetic data obtained from this study, however, suggests that in heavily nephrotic patients, rituximab dosed in this fashion results in patients being under-treated. The present study propose to test the hypothesis that rituximab, given in accordance to the standard lymphoma protocol 375mgm2 x 4, will result in a more effective and profound depletion of B cells, a more complete suppression of pathogenic antibodies, and a higher remission rate of the NS while maintaining a favorable safety profile. 