We investigated whether sodium butyrate, administered orally as gastroresistant slow-release pellets to rats, could affect markers of colon carcinogenesis. F344 male rats were fed a high-fat diet (230 g/kg corn oil, wt/wt) and treated with two injections (1 wk apart) of azoxymethane (15 mg/kg sc) or saline. Rats were then divided into two groups: one received the diet with 1.5% (wt/wt) sodium butyrate for 10 weeks to provide 150 mg butyrate/day, and one group received no butyrate. At the end of this period, rats were sacrificed, and colonic proliferative activity, number of aberrant crypt foci (ACF), and apoptosis were assessed in the colon. The proliferative activity and ACF induction were not affected by butyrate pellet administration. On the contrary, in rats treated with butyrate, apoptotic index increased from 0.12 +/- 0.12 to 0.81 +/- 0.10 (means +/- SE, p < 0.05). The short-chain fatty acid concentration was significantly increased in the feces of rats treated with butyrate. In conclusion, the increase in the mucosal apoptotic index suggests that gastroresistant butyrate pellets have a beneficial effect against colon carcinogenesis. However, because butyrate pellets did not modify proliferation or ACF induction, this conclusion should be confirmed in long-term carcinogenesis experiments.