Mate, L., Virkel, G., Lifschitz, A., Sallovitz, J., Ballent, M., Lanusse, C. Phase 1 and phase 2 metabolic activities along the small intestine in adult male sheep. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2010.01177.x. Metabolic activities of several xenobiotic metabolizing enzymes were evaluated in both hepatic and enteric subcellular fractions obtained from Corriedale × Merino crossbreed rams by using a biochemical approach. Microsomes obtained from the different segments of sheep small intestinal mucosa displayed cytochrome P450 (CYP)‐dependent N‐demethylations but not O‐deethylase activities apparently occurred. CYP‐mediated N‐demethylations neither decreased nor increased along the small intestinal mucosa. Percentages of activity for erythromycin N‐demethylase in the small intestine were between 29% (duodenum) and 45% (ileum) from that measured in the liver, whereas those determined for triacetyl‐oleandomycin N‐demethylation ranged between 10% (duodenum) and 15% (jejunum) of the same hepatic activity. Conversely, metabolic rates for aminopyrine and chlorfeniramine N‐demethylations in the gut mucosa ranged between 3% and 7% compared to their respective hepatic enzyme activities. Sheep enteric mucosa also displayed metabolic reactions typically mediated by flavin‐containing monooxygenases (FMOs), carbonyl reductases (CBRs), carboxylesterases (CES), glutathione S‐transferases (GSTs) and uridine diphosphoglucuronyltransferases (UGTs). The FMO‐mediated sulfoxidation of methimazole was 2.6‐fold higher (P