Epithelial cells of the gut are characterized by rapid, constant cell renewal. The death of epithelial cells at the villus tips occurs so regularly that it must be regarded as a well-controlled cell death, designated as apoptosis. However, only limited information has been available on the mechanism of this phenomenon, including the disposal of the effete cells. In the small intestine of the guinea pig and monkey, macrophages are densely aggregated at the lamina propria of the villus tips and vigorously engaged in the phagocytosis of effete epithelial cells. Intraepithelial lymphocytes possessing cytoplasmic granules, possibly intense in cytotoxicity, are topographically associated with the dying enterocytes, suggesting lymphocyte-mediated killing. After the engulfing of apoptotic enterocytes is left within the epithelium, maintaining the epithelial barrier until it is pinched off by the pushing of surrounding enterocytes. In the rat and mouse, on the other hand, effete enterocytes are exfoliated as a whole from the villus tips into the gut lumen. Macrophages, also numerous at the villus tips in these species, are less intense in phagocytotic activity. At the shoulder region of the villus, subepithelial macrophages extend thick processes deep into the epithelium; the processes appear to push out some enterocytes with typical apoptotic signs into the gut lumen. Lamina propria macrophages in the rat and mouse do not engulf enterocytes, but are believed to be involved in the induction of their apoptosis. The species difference in the mechanism of the apoptosis of enterocytes provides clues for understanding apoptosis.