This paper reports in vitro effects of individual heavy metals (Cd(2+), Cu(2+) and Hg(2+)), and PAHs, including benzo[a]pyrene(BaP), indeno[1,2,3-cd]pyrene (IP) and fluoranthene (FL), and their mixtures on ethoxyresorufin-O-deethylase (EROD) activities using a plate-reader method. The results showed that all three metals inhibited EROD activity, while BaP/IP significantly induced the enzyme. However, FL alone decreased EROD activity. Moreover, co-treatment with BaP/IP and heavy metals inhibited PAH-induced EROD activities, while combined exposure to FL and heavy metals induced FL-inhibited EROD activities.