1. Effects of short-chain fatty acids (SCFA) on epithelial proliferation of the intestine were studied in ileally fistulated rats fed on an elemental diet. 2. The stimulatory effect of daily doses of acetic, propionic and n-butyric acids (100, 20 and 60 mM respectively; pH 6.1) per fistula (3 ml, twice daily) on crypt cell production rate (CCPR) appeared within 2 d and lasted for at least 5 d. 3. The daily doses of SCFA for 14 d increased daily CCPR three to four fold. This effect was independent of the presence of gut bacteria. 4. Effects of SCFA were dose-dependent and varied among acids (butyrate greater than propionate greater than acetate). The effect was independent of low lumen pH. 5. In contrast, SCFA inhibited epithelial proliferation of isolated rat caecal tissue in vitro. 6. These results suggest that SCFA are physiological lumen trophic factors mediated by a systemic mechanism in vivo. 7. It is concluded that SCFA are involved in the trophic effects of gut microbes, ingestion of fermentable fibre, and lumen contents.