Aphthous lesions in the neoterminal ileum from patients operated for Crohn's disease are an early sign of recurrence that can be identified during ileocolonoscopy. The origin of these lesions was studied in nine patients treated by terminal ileal resection and right hemicolectomy for complicated Crohn's disease. During surgery the neoterminal ileum was turned inside out, the mucosa was carefully inspected and two large mucosal biopsies were obtained. The same procedure was carried out in seven patients operated for other diseases. Four to six months after surgery endoscopy of the neoterminal ileum was carried out and multiple biopsies were obtained from the neoterminal ileum. Another follow-up colonoscopy with biopsies was carried out one year after the operation. The operative specimens and the per- and postoperative biopsies were submitted to routine microscopy and immuno- and enzyme-histochemistry. None of the Crohn's patients had macroscopic lesions in the neoterminal ileum at operation and only one had microscopic signs of inflammation and a positive section margin. Four-six months after operation all Crohn's patients had active aphthous lesions in a 5-20 cm segment of the neoterminal ileum at endoscopy. Biopsies taken at this time showed microscopic features which were not observed in biopsies from control subjects: an increase of HLA-DR+, ATPase+ dendritic cells in the ileal mucosa and a defective expression of MHC class II antigens by the small intestinal epithelial cells. MHC class II expression by the small intestinal epithelial cells returned towards normal after one year.(ABSTRACT TRUNCATED AT 250 WORDS)