Forty-five patients with Crohn's disease in whom the upper gastrointestinal tract was normal by x-ray were examined by gastroduodenoscopy. Biopsies were analyzed histologically from the lower esophagus, body of the stomach, gastric antrum and duodenal bulb. Cell counts were made of 500 connective tissue cells of the duodenal mucosa. Histological examinations and cell counts of the duodenal mucosa were also performed on 50 healthy volunteers used as controls. Histological lesions were found in 19 Crohn's disease cases; 11 (24%) were considered pathologically diagnostic and all these were found in the antrum or duodenum. In 11 the mucosa was endoscopically normal. Granulomas were present in three cases (7%), all from normal appearing mucosa. Microscopic alterations of the antrum and duodenum, similar to findings in the normal appearing rectal mucosa, support the concept that Crohn's disease involves the entire alimentary canal and that lesions are seen grossly only where the disease is most advanced.