A scanning electron microscopic study of Crohn's disease was done using surgically resected specimens. Grossly normal resection margins as well as nonulcerated portions from diseased areas were selected for study. Scanning electron microscopic findings in Crohn's disease included changes in villous size and shape, villous fusion and epithelial bridge formation, goblet cell hypertrophy and hyperplasia, and increased secretion of mucus. These changes were marked in involved areas, and many were also present in six of seven margins of resection available for study in the ileal group. The abnormalities found in grossly normal margins of resection suggest a more widespread involvement than can be appreciated by gross and light microscopic examination of the specimen. Formation of the increased coat of mucus observed may be stimulated by a number of agents and could contribute to an enhanced barrier function in areas of early involvement in Crohn's disease, thereby decreasing the uptake of toxic or antigenic macromolecules. A decrease in bacterial superinfections would also be facilitated. Later lesions, with severe villous changes and hypersecretion of mucus, may favor the uptake of toxic and antigenic macromolecules as well as aid in the establishment of bacterial superinfections.