The effect of in vitro exposure to the metal ions (chromium (VI) and cobalt (II)) on phase I and phase II enzymatic activities in freshly isolated rat hepatocytes is reported. Concentrations of metal ions used reflect those reported in the livers of cadavers that had worn metal-on-metal hip implants. To assess the effect of exposure to metal ions on enzymatic activities of phase I metabolic reactions the hydroxylations of testosterone were measured, and the phase II reactions measured were glucuronidation and sulfation. No effect was observed in the formation of the testosterone metabolites measured in the presence of either ion, Cr (VI) inhibited both glucuronidation and sulfation of 7-hydroxycoumarin (7-HC) and 1-naphthol, while Co inhibited only the glucuronidation of 7-HC and 1-naphthol. ATP levels were reduced in freshly isolated rat hepatocytes treated with Cr (VI) compared with control hepatocytes with no metal treatment. Cr (VI) probably inhibits the formation of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the high energy co-factor of sulfation, by reducing the availability of ATP and also by acting as a substrate analog and competing with sulfate for ATP-sulfurylase. High concentrations of these metal ions in the livers of patients with loose or worn metal implants may act synergistically, and have consequences for the metabolism of xenobiotics.