We examined the response of the developing mouse intestine to X radiation using neonates (1 day postpartum), infants (2 weeks postpartum) and adults (7 weeks postpartum). Irradiated adult small intestinal crypts displayed two waves of apoptosis. The first wave peaked at 3 h and was followed by a broad wave with a peak persisting from 24 to 48 h. p53 was expressed during the first wave but not the second wave. For the infant small intestine, the intensity of the first wave was approximately half that of the adult wave, and for the colon the intensity was even smaller. In neonates, apoptosis was delayed, peaking at 6 h for small intestinal crypts and at 24 h for colonic crypts. Although no apoptosis occurred at 3 h postirradiation in neonates, p53 was present in both the small intestine and colon, owing at least in part to the inability of p53 to increase the level of Noxa, a p53-dependent pro-apoptosis protein, suggesting a discontinuity in the p53-Noxa-caspase pathway in neonates. By contrast, the induction of p21, a pro-survival protein, was greater in neonatal cells than in adult cells. Thus it appears that the developing and adult intestine mount distinct apoptotic responses to radiation.