Glutathione S-transferase and NAD(P)H: quinone oxidoreductase 1 enzymes have important roles in detoxification and also activation of a wide variety of chemicals. Moreover, resistance of tumor cells against chemotherapeutic agents has been implicated in GST activities. The aim of this study was to investigate the effect of polyphenolic compound tannic acid on rabbit liver and kidney glutathione S-transferase and NAD(P)H: quinone oxidoreductase 1 enzyme activities. Tannic acid was found to be a potent inhibitor of both hepatic and renal cytosolic glutathione S-transferase with an IC50 value of 0.33 mu M and 0.24 mu M, respectively. Tannic acid was shown to be a noncompetitive inhibitor of liver glutathione S-transferase and NAD(P)H: quinone oxidoreductase 1 with K-I of 0.4 mu M, and 16.5 mu M, respectively. In kidney, tannic acid was an uncompetitive inhibitor of glutathione S-transferase while it was noncompetitive inhibitor of NAD(P)H: quinone oxidoreductase 1 with a K-I of 12.6 mu M. Tannic acid may change the metabolism of a number of chemicals by modulating the enzymes involved in xenobiotics detoxification and/or activation pathways.