BACKGROUND Necrotizing enterocolitis associated with milk protein intolerance is rare. METHODS A girl, born at term, weighing 3,150 g, was fed several different formulas because of persistent vomiting and diarrhea; some of these formulas contained cow's milk proteins. At 5 weeks of age, the patient developed acute abdominal distension and obstructive manifestations. Laparotomy showed intestinal distension and perforation of the distal small bowel, requiring resection with temporary ileostomy. Histological examination of the resected segment of the small bowel showed extensive necrosis of the mucosa and submucosa with involvement of the muscular layers. The patient was given parenteral nutrition for 3 weeks then refed with human milk. Cow's milk was introduced at the age of 2 1/2 months; this was immediately followed by vomiting and an anaphylactic reaction, with increased ileostomy fluid volume and blood and sugars in stools. A jejunal biopsy performed 3 weeks later showed moderate villous atrophy with a dense infiltrate of eosinophils below the epithelium. The RAST test was positive to beta-lactoglobulin and negative to casein and lactalbumin. The patient tolerated cow milk by the age of 18 months. CONCLUSIONS Cow's milk protein tolerance should be evaluated when necrotizing enterocolitis occurs in the absence of classical risk factors.