Two patients presented with abdominal pain, diarrhea, and tender right lower-quadrant masses. Both patients had computerized tomographic scans showing cecal thickening and mass effects with multiple mesenteric lymph nodes and sparing of the rest of the colon. Colonoscopy in each patient also revealed disease confined to the right colon, and the mucosal pattern was consistent with that of Crohn's disease. The patients were both treated as having Crohn's disease until stool testing showed the presence of Escherichia coli O157:H7 serotype and follow-up computerized tomography scans and endoscopies revealed no evidence of chronic inflammatory bowel disease. E. coli O157:H7 is an increasingly recognized enteric infection, and these cases highlight how this infection may mimic right colonic Crohn's disease in its presentation. Furthermore, the submucosal nature of the clinical findings is discussed. Patients presenting with acute bloody diarrhea and displaying clinical and computerized tomographic features of Crohn's disease should have E. coli O157:H7 infection excluded before therapy for Crohn's disease is initiated.