Prevalence of heavy metals in the living environment causes chemical stress and reactive oxygen species (ROS) formation in Phanerochaete chrysosporium (P. chrysosporium). However, the mechanisms involved in ROS defense are still under investigation. In the present study, we evaluated the effect of lead- and cadmium-induced oxidative stress on the activities of catalase (CAT), peroxidase (POD), lignin peroxidase (LiP), and manganese peroxidase (MnP). A time-dependent change in all enzyme activities was observed following exposure to 50 mu M cadmium and 25 mu M lead. The lowest values were recorded at 4 h after exposure. Both cadmium and lead inhibited CAT and POD. The cytochrome P450 (CYP450) levels increased under 50-100 mu M cadmium or lead exposure and decreased when heavy metal concentration was under 50 mu M; this suggested that ROS is not the only factor that alters the CYP450 levels. The cadmium removal rate in the sample containing 900 mu M taxifolin (inhibitor of CYP450) and 100 mu M cadmium was reduced to 12.34 %, 9.73 % lower than that of 100 mu M cadmium-induced sample, indicating CYP450 may play an indirect but key role in the process of clearance of heavy metals. The pH of the substrate solution decreased steadily during the incubation process.