Our previous finding in the guinea pig that macrophages are aggregated at the villus tips of the small intestine and phagocytose effete enterocytes, in contrast to the accepted view that the enterocytes are exfoliated into the lumen, was extended in the present study to the large intestine of this animal and to the intestines of other mammals. In the large intestine of guinea pigs, aggregations of macrophages with an acid phosphatase activity were found beneath the epithelial lining, linearly surrounding the crypts. The macrophages contained debris of epithelial cells in their phagosomes, suggesting that the macrophages phagocytose apoptotic epithelial cells. This finding was supported by tracing BrdU-marked enterocytes, which were found to be taken up by the macrophages in the lamina propria. The macrophage aggregation was also recognized in the ileum of newborn guinea pigs, a finding favoring the idea that it represents a constant and intrinsic phenomenon and is not induced by penetration of foreign particles or other immunological events. In the monkey small intestine, macrophages with abundant phagosomes aggregated in large numbers in the lamina propria of the villus tips and were found to phagocytose enterocytes. In the hamster and rat, macrophages were numerous in the villi of the small intestine but they did not reveal images suggesting their involvement in the enterocyte removal. The mouse and rabbit showed only few macrophages with an acid phosphatase activity in the lamina propria of villi. The present finding in the monkey urges an investigation as to whether the novel mechanism of enterocyte disposition by subepithelial macrophages might be taking place in the human intestine.