In vivo methods provide several advantages for the study of metabolism relative to the commonly used in vitro techniques. The integrity of the organism and actual physiological conditions are maintained to reflect more accurately the processes occurring on exposure to a xenobiotic compound. Experimental precision is improved because each animal serves as its own control and can be used to generate a complete pharmacokinetic experiment. This may result in the added benefit that fewer experimental animals will be needed for a metabolic investigation using in vivo techniques. The technique of microdialysis perfusion was characterized for the in vivo study of the hepatic metabolism of phenol and conjugation by glutathione. In this study, in vivo experiments were conducted by implanting a microdialysis probe into the intact, in-place liver of a killed rat. These results were compared to in vitro experiments using liver homogenate and liver-microsomal protein. Substantial differences were observed between the in situ experiments and those performed in vitro.