Butyrate has induced differentiation in neoplastic cells grown in vitro, among them being colon cancer cell lines. In vivo, only one major study used sodium butyrate in the drinking water and showed an elevation in 1,2-dimethylhydrazine induced colon cancer in rats. Seeking to show that it was the sodium and not the butyrate which was responsible for the enhancement, we fed tributyrin at a 5% level to mice for 48 weeks. Mice experienced normal growth and development at this dose. Analysis of short chain fatty acids in the feces after 6 months in tributyrin feeding showed a 10-fold increase in butyric acid. However no difference in AOM induced focal areas of dysplasia or colonic tumor incidence was observed between tributyrin fed and control mice. At least two conclusions have been reached by this study, (1) that the dietary use of a sodium salt can contribute to the enhancement of chemically induced colon neoplasia and (2) butyrate may be discounted as providing any major therapeutic benefit against colonic tumorigenesis.