Surgically resected specimens and grossly normal resection margins from patients with Crohn's disease and normal controls were studied by a variety of ultrastructural techniques. This work describes changes in three anatomic barriers--mucus, cell coat, and epithelial cells--found in this disease. As seen by transmission electron microscopy, mucus was increased in diseased areas as well as in the margins of resection. The thickness of the cell coat was moderately increased in resection margins but not in diseased areas. Detachment and losses of cell coat were noted in some diseased areas. A marked increase in cytoplasmic dense vesicles suggests increased losses and increased production of cell coat in diseased areas. Goblet cells and epithelial cells showed no consistent signs of cell injury. Epithelial cells in diseased areas had markedly shortened microvilli and an increase in lysosomes. Paneth cells were increased in number and showed both focal granule extrusion and cytoplasmic lysosomal inclusions. The possible significance of these findings in terms of barrier function and uptake phenomena is discussed.