1-methyl-4-phenylpyridinium (MPP+) selectively destroys dopaminergic neurons and induces the symptoms similar to Parkinson's disease. The dopaminergic toxicity of MPP+ could be due to dopamine transporter (DAT) uptake and associated inhibition of mitochondrial complex I. The proposed mechanism of MPP+ toxicity is being investigated using MN9D and HepG2 cell models. Our studies show that both cells take-up MPP+ while only MN9D cells are susceptible to MPP+ toxicity. MPP+ toxicity is independent of DAT in MN9D cells. Extracellular calcium and voltage-gated calcium channel blockers decrease the MPP+ uptake into MN9D cells, but do not protect MN9D cells from MPP+ toxicity. These results suggest that the perturbation of intracellular calcium levels by MPP+ may be the cause of toxicity.