Lead (Pb2+) is a neurotoxic trace metal, widespread in aquatic environment that can change physiologic, biochemical and behavioral parameters in diverse fish species. Chemical exposure may drive modulation of mitogen-activated protein kinases (MAPKs) that are a family of highly conserved enzymes which comprise ubiquitous groups of signaling proteins playing critical regulatory roles in cell physiology. Extracellular signal-regulated kinases (ERK1/2) and p38(MAPK) control complex programs such as gene expression, embryogenesis, cell differentiation, cell proliferation, cell death and synaptic plasticity. Little information is available about MAPKs in aquatic organisms and their modulation by trace metals. The aim of this work was to determine the modulation of ERK1/2 and p38(MAPK) phosphorylation by Pb2+ in vivo and in vitro, in cerebellar slices of the catfish, Rhamdia quelen. In the in vitro model, slices were incubated for 3 h with lead acetate (1-10 microM). In the in vivo studies, the animals were exposed for 2 days to lead acetate (1 mg L(-1)). ERK1/2 and p38(MAPK) (total and phosphorylated forms) were immunodetected in cerebellar slices by Western blotting. Pb2+ added in vitro at 5 and 10 microM increased significantly the phosphorylation of both MAPKs. The in vivo exposed animals also showed a significant increase of ERK1/2 and p38(MAPK) phosphorylation without changes in the total content of the enzymes. In conclusion, the present work indicates that it is possible to evaluate the ERK1/2 and p38(MAPK) activation in the central nervous system (CNS) of a freshwater fish largely distributed in South America. Moreover, Pb2+, an important environmental pollutant may activate in vitro and in vivo ERK1/2 and p38(MAPK) enzymes. These findings are important considering the functional and ecologic implications associated to Pb2+ exposure of a freshwater fish species, such as R. quelen, and the roles of ERK1/2 and p38(MAPK) in the control of brain development, neuroplasticity and cell death.