Transmission electron microscopy was done using surgically resected 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 for viewing by a variety of techniques. Six hundred five Epon embedded blocks were studied by light microscopy, and 112 of these were viewed in the transmission electron microscope. Study of the immunologic inflammatory response revealed a number of changes of interest. The number of mast cells was markedly increased, and they were found predominantly in edematous submucosa and between smooth muscle cells in the muscular coats of the involved gut. Evidence of focal and complete degranulation of mast cells was frequently seen. Basophilic leukocytes, some of which had degranulated, were also identified. Another frequently encountered cell, the eosinophil, showed changes in the granules, which might reflect the release of eosinophil granule materials. Eosinophils also contained an increased number of small dense granules of the arylsulfatase containing type. Eosinophils, basophils, and mast cells formed close associations. Evidence of acute and chronic damage to vascular endothelia was present. Small lymphocytes, plasma cells, macrophages, and epithelioid cells were present. Multinucleated giant cells were infrequently encountered. Lymphoblasts, however, were rarely seen.