Collagenous sprue (CS) is a rare disease characterized by celiac type small bowel malabsorption that is resistant to gluten free diet (GFD) and is associated with a poor prognosis. Our aim was to assess the properties of the monoclonal TNF-alpha antibody infliximab in a patient with high-dose steroid refractory CS. A 27-year-old man developed watery diarrhea with weight loss and abdominal pain. Duodenal biopsies showed a subtotal villous atrophy with an extensive subepithelial layer of collagenous fibers. An apparent GFD did not reduce symptoms. High dose steroid treatment (75 mg prednisone) in combination with azathioprine (150 mg) reduced diarrhea but did not induce complete remission. Based on strongly elevated mucosal TNF-alpha transcript concentrations we introduced infliximab (5 mg/kg body weight) into therapy. After two applications the patient's symptoms quickly improved. During the following year no recurrence of diarrhea has been observed. This case suggests that infliximab is an effective treatment in complicated cases of collagenous sprue.