Cadmium is a non-physiological heavy metal released into the environment and workplace as a result of industrial, municipal, and agricultural activities. The association of Cd with pulmonary, prostatic and testicular cancer may be related to the ability of Cd to induce oxidative stress, which could in turn cause oxidative damage to DNA. This study examines the response of antioxidant enzymes and metabolites to Cd-induced oxidative stress in normal liver cells. We found a definite concentration-dependent increase in ROS when CRL-1439 normal liver cells were exposed to various concentrations of Cd2+ (100-300 microM). An increase in ROS production is an indication of oxidative stress, which is known to impact on the performance of antioxidant enzymes and metabolites in the cell. In fact, we found that superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPx) lost activities upon a 4-h exposure of liver cells to levels of Cd2+ ranging from 100 to 300 microM. After exposure of cells for 8 h, the activity of SOD and GPx increased while those of CAT and GR decreased substantially. The metabolites glutathione (GSH), oxidized glutathione (GSSG) and total thiols showed a decrease in concentration after 4 or 8 h of incubation of liver cells with Cd (100-300 microM). Malondialdehyde (MDA) on the other hand, showed an increase in concentration after 4-8 h of incubation of liver cells with Cd due to lipid peroxidation. The relationships of these fluxes to oxidative stress as well as intracellular redox homeostasis are discussed.