A method for producing macroscopic epithelial nodules was developed in order to investigate the properties of epithelial stem cells in the large intestine of mice. The cecum was exteriorized and exposed to various doses of X-ray radiation. Numbers of nodules subsequently developing were counted and plotted against radiation dose. From the logarithmic regression line, the susceptibility to irradiation of nodule-forming stem cells (NFSC) was determined. The susceptibility of cecal NFSC was comparable to the value reported for jejunal NFSC. Mice of (C57BL/6 x DS) F1-Pgk-1b/Pgk-1a that carried X-chromosome inactivation mosaicism for the phosphoglycerate kinase gene were used for examination of nodule clonality. Most cecal nodules contained only 1 type of phosphoglycerate kinase, suggesting a monoclonal origin of the nodules. Histochemical studies showed the presence of absorptive epithelial, goblet and entero-endocrine cells in 17-day-old nodules, implying multipotentiality of the NFSC. In spite of these similarities between cecal and jejunal NFSC, the macroscopic appearance of cecal nodules was quite different from that of jejunal nodules. Only crypt-like structures were observed in the former, whereas both crypt-like and villus-like structures were present in the latter. A comparison between cecal and jejunal nodules may be useful for understanding the morphogenesis of the intestinal mucosa.