Transmission electron microscopy was done on surgical specimens from 12 patients with Crohn's disease and three control subjects. Nonulcerated involved areas of ileum as well as proximal, grossly uninvolved resection margins were chosen for study. Specimens for transmission electron microscopy were prepared by a variety of techniques and 112 blocks were examined by electron microscopy. The study was concentrated on two target tissues of the gut: the autonomic nervous system and the smooth muscle. Proliferative and injurious changes were found in each. Proliferation, myofibroblastic transformation, hypercontraction, and necrosis characterized the smooth muscle changes seen in Crohn's disease of the ileum. Autonomic nervous system changes included proliferation of axons containing dense core granules (catecholamines) and axonal necrosis. The possible pathogenetic significance of these changes is discussed here and in the accompanying article beginning on page 606 of this issue.