Transmissible murine colonic hyperplasia was examined ultrastructurally by sequential sampling after inoculation with the etiologic agent, Citobacter freundii. Light-microscopic changes in the descending colon of inoculated mice were correlated with scanning and transmission electron-microsopic findings. Bacteria were attached to the surface of the mucosa between 4 and 10 days after inoculation. Hyperplasia was most severe at 16 days and thereafter underwent regression. Regression was preceded by extrusion of infected cells from the surface mucosa and replacement by immature hyperplasia epithelium. Hyperplastic epithelium throughtout the crypt resembled undifferentiated crypt cells of controls. By 45 days, the mucosa had reverted to near normal structure. The results suggest that severe mucosal proliferation with minimal inflammatory change resulted from attachment of bacteria to the surface mucosal epithelium. The hyperplastic response appeared to be a defense mechanism of replacing infected cells with newly migrated, uninfected epithelium.