Two young adult male Domestic Shorthair cats living in the southeastern United States were evaluated for signs attributable to partial intestinal obstruction. Physical examination indicated a palpable abdominal mass in each animal. Exploratory laparotomy revealed a large extraluminal mass involving the ileum and mesentery with adjacent mesenteric lymphadenopathy in cat No. 1 and an abscessed mass in the distal duodenum in cat No. 2. Mass resection and intestinal anastomosis were performed in both cats. Histologic evaluation indicated that the intestinal lesions involved primarily the outer smooth muscle layer and serosa and consisted of eosinophilic granulomatous inflammation with multifocal areas of necrosis. In Gomori methenamine silver-stained sections, broad (2.5-7.5 microm), occasionally branching, infrequently septate hyphae were observed within areas of necrosis. A diagnosis of Pythium insidiosum infection was confirmed in both cats by immunoblot serology and by immunoperoxidase staining of tissue sections using a P. insidiosum-specific polyclonal antibody. Cat No. 1 was clinically normal for 4 months after surgery but then died unexpectedly from an unknown cause. Cat No. 2 has been clinically normal for at least 9 months after surgery and appears to be cured on the basis of follow-up enzyme-linked immunosorbent assay serology.