The crypts of the gastrointestinal mucosa are highly structured and polarised organs with rapid cell proliferation and an hierarchical organisation with relatively few stem cells. These tend to be located at specific positions in the tissue--at the crypt base in the colon and about four cell positions from the base (above the Paneth cells) in the small intestine. A small but constant level of spontaneous cell death occurs in the crypt. The levels of cell death are elevated by small exposures to radiation or cytotoxic drugs. The morphology of the cell death is typical of apoptosis. The maximum yield of cell death following cytotoxic exposure is observed at about 3-6 h after treatment and for many agents the death is characteristically located at the fourth (stem) cell position in the small intestine. The significance and implications of these observations are discussed in relation to the internal screening and programming within damage cells and with respect to tissue homeostatic mechanisms.