The protective effect of trihexyphenidyl (THY) on hydrogen peroxide-induced oxidative damage was investigated in the rat pheochromocytoma line PC12 cells. Following the exposure of PC12 cells to H(2)O(2), there was a reduction in cell survival, activities of superoxide dismutase (SOD) and mitochondria membrane potential (MMP), in contrast, the increased levels in Lactate dehydrogenase (LDH) release, malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS), as well as intracellular [Ca(2+)]i level were observed. However, preincubation of cells with THY prior to H(2)O(2) exposure attenuated all the changes mentioned above, THY exhibited protective effect against H(2)O(2)-induced toxicity in PC12 cells, indicating that the compound may be a potential therapeutic agent for the diseases influenced by oxidative damage.