Methyl-Mercury (MeHg) has been pointed as an important environmental contaminant and presents many toxic effects on animals and humans. MeHg toxicity involves multiple biochemical mechanisms. However, there is a lack of information regarding cell signaling pathways involved in its toxicity. The aim this study was to investigate, in hippocampal slices, the modulation of cell viability and P38^MAPK phosphorylation by MeHg. The hippocampal slices of immature Wistar rats (14 days old) were incubated for 2 h in the presence of MeHg (10-100 mM). The cell viability was assayed by MTT test. The P38^MAPK phosphorylation was analyzed by western blotting. The results indicate that MeHg caused a significant decrease in cell viability assessed by MTT, at concentrations of 30 and 100 mM. The P38^MAPK phosphorylation was increased in response MeHg treatment at 10 and 30 mM. The total P38^MAPK content was not altered by MeHg incubation. In conclusion, our results suggest a possible involvement of P38^MAPK pathway on the neurotoxicity of MeHg. Further experiments are needed to clarify this hypothesis. Support: CNPq, CAPES, PROCAD, UFSC.