Colon carcinoma was implanted into the mesenterium of syngeneic BD IX rats, and 10 weeks later the animals were fasted for 48 h and refed. Control animals were kept fasted for an additional 24-h period. DNA synthesis was measured in mucosal scrapings from the normal colon and in the tumor before and after refeeding. Autoradiography was used to determine the epithelial DNA synthesis index (labeling index) in the progenitor cells from normal colon mucosa, in the adenocarcinoma cells from the tumor, and in the tumor lymphocytes. DNA synthesis increased over control values in the normal mucosa in situ (p less than 0.01), and in the implanted tumor (p less than 0.05) at 16 h after refeeding. The labeling index also increased over control values in the progenitor cells from normal mucosa (p less than 0.01), and in the adenocarcinoma cells from the tumor (p less than 0.01) at 16 h after refeeding. No increase in labeling index was observed in the tumor lymphocytes. These data suggest that cell proliferation in normal colon epithelium as well as in colon adenocarcinoma cells may be stimulated by a common physiological factor released after feeding.