It is well known to carbohydrate chemists that substituted sugars may undergo facile rearrangement involving the migration of the aglycone from --OH to adjacent --OH. Despite the importance of glycoside conjugates, notably involving glucuronic acid, in the metabolism of xenobiotics, drug metabolism workers have neglected this phenomenon. The potential rearrangement of glucuronides from the biosynthetic C-1 isomers to other positional and stereo-isomers is important, since only 1-O-substituted beta-D-glucosiduronates are substrates for beta-glucuronidase, which is commonly used to identify such conjugates. The intramolecular rearrangement of clofibryl glucuronide has been studied over the pH range 5.2-8.6, by enzymic hydrolysis with beta-glucuronidase, and by HPLC. The amount of clofibric acid released from the conjugate by beta-glucuronidase falls with increasing pH of preincubation above pH 7.4, and this is accompanied by the appearance of three new peaks, each containing both clofibric and glucuronic acids, in the HPLC traces of the incubation mixtures. Similar experiments with three other glucuronides, those of p-nitrophenol, phenolphthalein and 7-hydroxycoumarin, did not show any conversion to beta-glucuronidase resistant forms. The phenomenon of intramolecular rearrangement of ester glucuronides must be considered whenever beta-glucuronidase is used in the analysis of conjugates of carboxylic acids.