Short chain fatty acids [SCFA: acetate 75, propionate 35, butyrate 20 (microM)] introduced intraluminally into the colon increased the mitotic index and the labeling index of the large intestinal epithelial cells within 60 min in fasted rats. 2. Epithelia that lacked direct contact with SCFA were also stimulated. 3. SCFA did not have such a stimulatory effect either in vagotomized rats or in sympathectomized rats. 4. These results suggest that SCFA stimulate epithelial cell proliferation in the large intestine of fasted rats via the autonomic nervous system.