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Background: Gastrointestinal hypersensitivity to cow milk (CM) may be more common among school-aged children and young adults than previously thought., Objective: The objective was to study various gastrointestinal complaints and the immunologic mechanisms associated with food-related, especially CM-related, gastrointestinal disorders in young adults., Design: Of 827 subjects aged 16-21 y who completed a questionnaire on food-related gastrointestinal symptoms, 49 symptomatic subjects agreed to a clinical examination, including an interview, blood tests, a lactose-maldigestion test, a blinded CM challenge and, in severely symptomatic subjects (n = 12), an endoscopic examination. Twenty-nine subjects served as controls., Results: Approximately 10% of the subjects reported having major gastrointestinal symptoms, mainly food-related (n = 70 of 86), during the preceding year. Specific organic disease was found in 2 symptomatic subjects: 1 case of celiac disease and 1 of colitis. The result of the lactose-maldigestion test was positive in 16 of the remaining 47 symptomatic subjects, but only 4 carried the C/C(-13910) genotype for adult-type hypolactasia. The symptomatic subjects had restricted their consumption of certain foods, particularly CM. However, in a blinded challenge, CM-induced symptoms were rare. The symptomatic subjects had higher plasma soluble intercellular adhesion molecule 1 (P = 0.007) and lower granzyme A (P = 0.001) concentrations than did the control subjects. Duodenal biopsy samples tended to have higher intraepithelial CD3(+) cell counts (P = 0.065) and a higher expression of transforming growth factor beta (P = 0.073) and interleukin 12p35 messenger RNA (P = 0.075) than did the control subjects., Conclusions: In an unselected cohort of young adults, 8% reported food-related gastrointestinal symptoms. The finding of immunologic activity implied the existence of a food-related gastrointestinal syndrome but not one induced by CM.