An alteration in the host response to the intestinal protozoan Spironucleus (Hexamita) muris was noted in x-irradiated rat small intestine. When few were present in the crypt lumina, the intestinal microvillar border was normal. However, when larger numbers were present, the microvilli were greatly reduced in numbers or entirely absent in some regions. The organism was identified in the base of the crypt lumen, in apical portions of mucous cells, and near the basement membrane. Spironucleus enclosed by digestive vacuoles occasionally appeared to be in the process of being extruded through the basement membrane. Not all intracellular protozoa were surrounded by such digestive vacuoles. Spironucleus was never seen in association with the digestive vacuoles of Paneth cells. Since it has been suggested that Paneth cells have a role as a fixed phagocyte, ingesting protozoa and other microorganisms, the results presented here suggest that this function may have been impaired in irradiated animals.