One of the most recent hypotheses concerning the protective effect of some dietary fibres against colon cancer implicates butyrate. Very few publications have addressed its possible influence on the phase II enzymes and on the bacterial enzymes involved in the enterohepatic recirculation of toxic compounds. We used an original model of monoxenic rats oriented towards the preferential production of butyrate. Fischer male germ-free rats were mono-associated with a strain of Clostridium paraputrificium. They were fed either a control diet or a lactulose-enriched diet for 6 weeks. In the cacco-colon the specific activities (SAs) of the microsomal enzymes (glutathione-S-transferase and UDP-glucuronosyl-transferase) were 1.7-fold those of the control rats. In the intestine and liver the SAs of the phase II enzymes were not altered, nor was the hepatic cytochrome P450. In the caecum of the lactulose-fed rats the SA of beta -glucuronidase decreased by 27% and that of beta -glucosidase doubled. The chronic consumption of lactulose doubled the total caecal short-chain fatty acids, and the production of butyrate was enhanced. Since the germ-free rats behaved differently when fed the same diets, we concluded that the fermentation products of lactulose (and not the lactulose itself) were involved in the effects we describe. The involvement of butyrate in this phenomenon is discussed. (C) 2001 Society of Chemical Industry.