The ultrastructure of Paneth cells of African giant rats (Cricetomys gambianus), which were captured on the savanna in western Africa, was studied. The Paneth cells of Cricetomys were clustered at the bottom of crypts of the small intestine, but not of the colon. In the normal state, Paneth cells had a few secretory granules showing high electron density. Small clear vesicles which are a characteristic in laboratory albino rats were not conspicuous. Vacuolated Paneth cells and secreted materials from the Paneth cells were frequently found. This suggests that the secretion of Paneth cells of Cricetomys is active in the natural state. No phagocytotic figures were observed. After atropine sulfate treatment, secretory granules increased in size and number, whereas the electron density decreased, similar to that of goblet cell granules. However, the granules were not stained by alcian blue or by PAS. Inhibition of secretory stimuli by atropine can alter the intracellular processing of secretory substances in Paneth cells.