1. The effects of tangeretin, green tea flavonoids, and other flavonoids on 7-ethoxyresorufin-O-deethylase (EROD; 450 1A), 7-pentoxyresorufin-O-dealkylase (PROD; P450 2B), p-nitrophenol hydroxylase (PNPH, P450 2E1), and erythromycin-N-demethylase (ERDM; P450 3A) were examined in induced rat liver microsomes. EROD, PNPH, ERDM, and nifedipine oxidase (NIFO; P450 3A4) were examined in human liver microsomes. 2. All flavonoids tested inhibited EROD activity at higher concentrations in liver microsomes. Flavone and tangeretin were potent inhibitors of EROD, with IC50's of 0.7 and 0.8 microM respectively in rat liver microsomes and 0.15 and 16 microM respectively in human liver microsomes. The green tea flavonoid (-)-epicatechin-3-gallate (ECG) was the most potent inhibitor of EROD in human liver microsomes (IC50 = 75 microM). The effect of the green tea flavonoids on EROD was complex; in addition to inhibition at high concentrations of flavonoid, moderate activation was seen at lower concentrations. 3. 450 2B-, 2E1- and 3A-dependent activities in rat and human liver microsomes were only moderately inhibited by any of the flavonoids tested, and, in general, ECG was the most potent inhibitor for these activities with IC50's ranging from 75 to 300 microM. 4. Tangeretin inhibited EROD activity (P450 1A2) in human liver microsomes in a competitive manner with a Ki = 68 nM. Tangeretin inhibited NIFO activity (P450 3A4) in human liver microsomes in an uncompetitive manner with Ki = 72 microM.