Retroperitoneal fibrosis (RPF) is an uncommon collagen vascular disease characterized by a chronic nonspecific inflammation of the retroperitoneum, which can entrap and obstruct retroperitoneal structures. Although obscure, an autoimmune-mediated or vasculitic etiology has been hypothesized. In the current report, a case of RPF associated with the presence of antibodies against proteinase III, which responded effectively to immunosuppressive therapy, is presented.