Oxidative stress is a critical route of damage in various psychological disorders such as schizophrenia, although fish oil and risperidone (RISP) induce antioxidant effects in the human body. However, the mechanisms behind these effects remain elusive. We investigated the effects of fish oil and RISP in the PC12 cell line by evaluating Ca(2+) mobilization, lipid peroxidation (LP) and antioxidant levels. PC12 cells were divided into eight flasks: control, fish oil, RISP, H(2)O(2), fish oil + H(2)O(2), RISP + H(2)O(2), fish oil + RISP and fish oil + RISP + H(2)O(2). Cells were incubated with fish oil and RISP for 24 and 48 h, respectively. Then, cells were exposed to H(2)O(2) for 15 min before analysis. Ca(2+) release and LP levels were higher in the H(2)O(2) group than in the control, RISP and fish oil groups, although their levels were decreased by incubation of cells in fish oil and RISP. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in the H(2)O(2) group than in the control, RISP and fish oil groups, although levels were higher in cells incubated with fish oil and RISP than in those in the H(2)O(2) groups. In conclusion, these results indicate that RISP and fish oil induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca(2+) release and antioxidant levels.