The mucosa of the ileum or colon from 16 patients with active Crohn's disease was studied using transmission electron microscopy of thin sections, scanning electron microscopy, and freeze fracture electron microscopy. Electron micrographs of diseased tissue, as well as of grossly normal resection margins, were studied. Correlations of mucosal disease, as seen with the various ultrastructural techniques, were made and compared to controls. Alterations of epithelial cell tight junctions in freeze fracture replicas correlated with a decrease in the number of pinpoint contacts between adjacent cells in transmission electron microscopy preparations. Gap junctions in Crohn's disease did not vary with respect to structure or number, when compared to controls. Mucosal microulcerations, affecting 1 to 6 cells, were observed in transmission and scanning electron microscopy preparations. Possible freeze fracture electron microscopy correlates of microulcers consisted of replicas of cells completely devoid of tight junctional structures. "Aphthoid" type ulcers were studied with the various ultrastructural tools and were remarkable for several abnormalities of villi bordering the aphthoid ulcers, as well as surrounding villi. Transmission, scanning, and freeze fracture electron microscopy each provide unique and confirming data that may be used to construct a model for the pathophysiology of Crohn's disease.