We have recently had a case of immediate post transplant recurrence of FSGS in a child that failed to respond to MMF, steroids, long-term plasmapheresis and conversion from tacrolimus to cyclosporine. The FSGS associated proteinuria however completely resolved at about 6 months after treatment of post transplant lymphoma with 6 doses of rituximab. A similar case that also resolved after treatment of PTLD with rituximab was recently reported. While the mechanism of action of both cyclosporine and MMF is unknown in FSGS, both drugs have been shown to have activity against B cells. The response seen in these two recent cases following treatment with a B cell specific agent leads to the hypothesis that at least some cases of FSGS have an autoimmune mechanism in which B cells play a central role. We propose to test this hypothesis by the treatment of patients with recurrent or primary persistent FSGS with rituximab.