Exposure to methyl mercury (MeHg), induces blood-brain barrier damage leading to non-selective influx of cytotoxic agents, besides the entrance of inflammatory cells into the brain. However, there is no data available regarding the effects of co-treatment of neopterin and interferon-gamma (IFN-gamma) in MeHgexposed SH-SY5Y dopaminergic neurons. MeHg- exposed SH-SY5Y human neuroblastoma cells were treated with neopterin and IFN-gamma in the presence and absence of L-Glutamine. Cell viability was determined by MTT assay. Oxidative stress intensity coefficient was calculated by taking into consideration the amount of nitric oxide production per viable neuron. 5 mu M MeHg was found to be more toxic than 1 mu M or 2 mu M doses of MeHg for SH-SY5Y cells in glutamine-containing medium. Furthermore, 0.1 mu M neopterin supplementation significantly increased the neuronal cell viability while, oxidative stress significantly decreased. Glutamine supplementation in culture medium, not only enhanced the MeHg toxicity, but also supported the antioxidant effect of neopterin. These results indicate that neopterin has a protective effect on MeHg toxicity in SH-SY5Y neurons. Neopterin was more effective in improving the total mitochondrial metabolic activity of cells exposed to 5 mu M MeHg in comparison to IFN-gamma. Although IFN- gamma supplementation alone partially improved 5 mu M MeHg toxicity on neurons, it weakened the protective effect of neopterin.