The major postprandial factors known to influence epithelial cell proliferation in the colon are intraluminal factors. In this study, a transverse colostomy was created in rats in order to avoid the intraluminal stimulation of the distal colon after feeding. After a 48-h fasting period, the animals were refed whereas controls were kept fasted. Refed animals with their controls were killed at respectively 0, 8, 12, 18, and 24 h after the time of refeeding. Autoradiography of in vitro labeled mucosal samples was used for determining the proliferative parameters in the colonic crypts. The uptake of [3H]thymidine in mucosal scrapings was measured for estimating DNA synthetic activity. Refeeding increased the labeling index of the crypts (p less than 0.01) and the mucosal DNA synthesis (p less than 0.01) not only in the proximal colon but also in the excluded distal colon. The increase in labeling index was followed by a significant mitotic peak in both segments. These data indicate that direct intraluminal stimulation is not the only mechanism involved after feeding. There are other potent physiological stimulants of epithelial cell proliferation in the colon which are released postprandially.