Introduction: Experimental studies of radiation damage to the intestine have thus far been concerned with cell death and disturbance of cell renewal (see Patt and Quastler, 1963; Braun, 1963; Bond, Fliedner and Archambeau, 1965; Cottier, 1966; Fry et al., 1969; Lesher and Bauman, 1969; Oehlert, 1969; Maisin et al., 1971). The purpose of our experiments was to study the radiation induced change of the functional epithelium of the intestinal villi in the early postirradiation phase by the histochemical demonstration of alkaline phosphatase as marker enzyme. Material and Methods: Adult male mice (C3H × 101 hybrides) received a single abdominal exposure to X-irradiation (1,200 rads). The animals were sacrified between 1 and 10 days after irradiation. The histochemical demonstration of the alkaline phosphatase with the azo dye coupling technique has been applied to gross preparations of the formalin-calcium (5°C) fixed whole small intestine ( Jervis, 1965) and to sections of the ileum: fresh frozen sections post-fixed with formalin-calcium, frozen sections and paraffine sections after rapid embedding ( Wolman, Spicer and Burstone, 1964) of formalin-calcium (5°C) fixed material. Alkaline phosphatase was simultaneously demonstrated with incorporated 3H-thymidine in autoradiograms according to Eder (1964). Results: Macroscopic and microscopic specimens show a complete loss of alkaline phosphatase activity in the villus epithelium of the ileum between 3 and 4 days after irradiation. The epithelial cells of the villi which are devoid of alkaline phosphatase also are not labelled with 3H-thymidine applied one hour before irradiation. The pattern of recurrence of enzyme active cells in the villi conforms to the pattern of cell regeneration observed with 3H-thymidine in the crypts at 4 to 5 days after irradiation. 7 days after irradiation the alkaline phosphatase reaction shows in the ileum a normal picture. Discussion: Our results show that the epithelial cells continue to migrate from the crypts to the villi after irradiation. The disappearance of alkaline phosphatase leading to a minimum at 3 to 4 days after irradiation is interpreted to reflect a disturbance of cellular differentiation which normally starts before the cells leave the crypts.