Reabsorption of the products of bacterial metabolism into the portal circulation provides the potential for an enterohepatic circulation of the compound. A consideration of the metabolism of xenobiotics performed by the gut flora shows that the major reactions are hydrolyses and reductions and thus these figure prominently in enterohepatic circulations. Foreign compounds which undergo enterohepatic circulation as glucuronides may be subdivided into those involving the parent compound and those involving oxidative metabolites. Enterohepatic circulation can be confirmed by the infusion of bile containing radioactive metabolites collected from one animal into the duodenum of a second animal. Comparison of the fate of the compound in normal and germfree animals provides the definitive proof of bacterial involvement in an enterohepatic circulation. The gut flora are an essential part of the enterohepatic circulation of many pharmacologically and toxicologicaly active compounds. An enterohepatic circulation can prolong the duration of drug action and thus may contribute to the effects produced, especially during chronic administration.