Ultrastructural studies of the colon epithelium of normal C57Bl/Ha and ICR/Ha mice revealed some unique characteristics not seen in human or rat colon. The most striking feature was the presence of a unique type of intracytoplasmic organelle with crystalline internal structure. These organelles measured 1-2 micron in diameter, usually rounded or oval showing marked variation in size and shape. They were surrounded by a single layer of trilaminar plasma membrane and their core structure was mildly electron dense with markedly dense crystalline substructure. Grimelius silver stain done at ultrastructural level revealed these to have staining properties identical to neuroendocrine granules. Approximately 1-5% of the epithelial cells of mouse colon were usually filled with these organelles. But occasionally they were also present in the endocrine cells of colon. The other striking feature of the mouse colon epithelium is the presence of an inordinate number of bacteria. These rod shaped bacteria were present deep inside crypts in large numbers. They were also present within the goblet type of mucous cells and the so-called columnar cells of the surface epithelium. A third unique feature of mouse colon was the presence of mitotic figures in cells with conspicuous mucous vacuoles. This contrasts with human and rat colon where mitosis occurs in cells with little or no mucus. Since the ultrastructural morphology of the normal mouse colon is distinctly different from the human and rat, caution must be exercised in extrapolating colon carcinogenesis data from mouse to human.