The aim of this study was to develop an animal model for necrotizing enterocolitis (NEC). Twenty-five neonatal Hanford minipigs had carotid artery and external jugular vein catheters and rectal Clinical Tonomitors placed under anesthesia. Experimental animals were subjected to a hypoxic insult (50% reduction in baseline PaO2 for 30 minutes) and hypothermic stress (core temperature reduced to 35 degrees C for 30 minutes). Regular oral diet was resumed and the survivors were euthanized 3 to 4 days later. All animals underwent necropsy with gross and histopathological evaluation of the entire bowel. Of 22 experimental animals, 14 survived (64%) and 8 (36%) died of pulmonary hemorrhage. Of the 14 survivors, 8 (57%) had gross and microscopic evidence of NEC. Six of the total 25 animals (24%) sustained rectal perforations from the tonometer. Of 3 control animals, one died of pulmonary hemorrhage and the two survivors had normal intestine. This model successfully produced gross and histological evidence of NEC. The tonometer shows promise as a predictor of NEC provided technical modifications can reduce the complication rate.