Butyrate is produced in the colon of mammals as a result of microbial fermentation of dietary fiber, undigested starch, and proteins. Butyrate may be an important protective agent in colonic carcinogenesis. Trophic effects on normal colonocytes in vitro and in vivo are induced by butyrate. In contrast, butyrate arrests the growth of neoplastic colonocytes and inhibits the preneoplastic hyperproliferation induced by some tumour promoters in vitro. We speculate that selective effects on G-protein activation may explain this paradox of butyrate's effects in normal versus neoplastic colonocytes. Butyrate induces differentiation of colon cancer cell lines. It also regulates the expression of molecules involved in colonocyte growth and adhesion and inhibits the expression of several protooncogenes relevant to colorectal carcinogenesis. Additional studies are needed to evaluate butyrate's antineoplastic effects in vivo and to understand its mechanism(s) of action.