The gastrointestinal tract is essential to host defence, acting as a barrier to absorption and translocation of gut antigens, including bacteria. In experimental models, protein malnutrition is permissive to gut barrier failure and endogenous infection. A clinical correlate has not been described. Intestinal morphology and barrier function to food protein antigens was studied in malnourished patients. Thirty-five individuals were evaluated, 20 malnourished patients and 15 well nourished hospital controls. Morphology was assessed from endoscopic biopsies of the second part of the duodenum, and serum immunoglobulin (Ig) G antibodies to gliadin and beta-lactoglobulin were measured. No antibody to food proteins was evident in the control group. In contrast, serum IgG antibodies to at least one antigen were present in 15 malnourished patients and to both antigens in ten (P < 0.0001 versus controls). Severely malnourished patients were more likely to have both antibodies present than those with mild or moderate malnutrition (P < 0.05). Antibody-positive malnourished patients had significantly better nutritional status than antibody-negative patients with malnutrition (P < 0.05). In no group of patients was there morphological evidence of abnormal mucosa or an immunological infiltrate. Gut barrier function is compromised in malnourished patients which suggests a mechanism that may facilitate gut-derived infection and sepsis.