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We describe 2 cases of multifocal idiopathic fibrosclerosis treated successfully with cyclosporine. The first patient presented with chronic abdominal pain and was subsequently found to have retroperitoneal fibrosis with ureteral obstruction. Other findings included cholangiolar fibrosis, retroorbital pseudotumors, submandibular gland enlargement, subcutaneous fibrotic masses, and elevated erythrocyte sedimentation rate (ESR) and serum creatinine. He initially responded well to temporary ureteral stenting followed by combination therapy with steroids and cyclosporine. He relapsed when cyclosporine was stopped, but subsequently remitted completely when cyclosporine was reintroduced. The second patient presented with long-standing abdominal pain with retroperitoneal fibrosis, submandibular gland enlargement, and an enlarged pancreas with a localized mass, all of which improved significantly with 6 months of therapy with cyclosporine. Cyclosporine was well tolerated with no significant side effects in the 2 patients. A review of the literature is presented.