Presented is an in vivo animal model of necrotizing enterocolitis (NEC) in which we used an isolated loop of rabbit colon. Changes in mucosal perfusion and macroscopic and microscopic appearances were studied after exposure of the mucosa to different intraluminal tensions and pHs. Mucosal perfusion was reduced with increasing intraluminal tension and decreasing pH. Histologic changes consistent with NEC were identified after five hours when the mucosa had been exposed to both increased intraluminal tension and decreased pH. Factors affecting intraluminal tension and pH could influence the development of NEC in the neonate.