OBJECTIVES: Functional gastrointestinal disorders (FGIDs) are common in children. Their pathogenesis remains unknown and is most likely multifactorial. We hypothesized that noninfectious causes of inflammation affecting the gastrointestinal (GI) tract early in life, such as cow's-milk allergy (CMA), can predispose to the development of FGIDs later in childhood. PATIENTS AND METHODS: Case-control study. Subjects were patients between 4 and 18 years diagnosed with CMA in the first year of life at Children's Memorial Hospital in Chicago, IL, between January 2000 and June 2009. Diagnosis of CMA was based on history and clinical findings. Siblings 4 to 18 years of age without a history of CMA were selected as controls. Cases completed the parental form of the Pediatric Gastrointestinal Symptoms Rome III version questionnaire to assess for GI symptoms. RESULTS: Fifty-two subjects (mean age 8.1 +/- 4.48 years, 62% girls) and 53 controls (mean age 9.7 +/- 4.20 years, 55% girls) participated in the study. Twenty-three of 52 subjects (44.2%) reported GI symptoms that included abdominal pain, constipation, or diarrhea compared with 11 of 53 controls (20.75%) (odds ratio 3.03, P = 0.01). Abdominal pain was significantly more common in cases (16/52, 30.8%) versus controls (5/53, 9.43%) (odds ratio 4.27 [1.43-12.7]) (chi(2) = 7.47, P = 0.01). Abnormal stool habits were more common in cases (15/52, 28.8%) versus controls (7/53, 13.2%), but the difference was not statistically significant. Ten of 52 subjects (19.2%) met the Questionnaire on Pediatric Gastrointestinal Symptoms Rome III version criteria for diagnosis of an FGID (7 irritable bowel syndrome, 2 functional dyspepsia, 1 functional abdominal pain), whereas none in the control group did. CONCLUSIONS: CMA constitutes a risk factor for the development of FGIDs in children.