Although the pathophysiological processes involved in dopamine (DA) neuron degeneration in Parkinson's disease (PD) are not completely known, apoptotic cell death has been suggested to be involved and can be modeled in DAergic cell lines using the mitochondrial toxin 1-methyl-4-phenylpyridinium (MPP super(+)). Recently, it has been suggested that histone deacetylase inhibitors (HDACIs) may reduce apoptotic cell death in various model systems. However, their utility in interfering with ABABABcell death remains unclear. The HDACIs sodium butyrate (NaB), valproate (VPA) and suberoylanilide hydroxamic acid (SAHA) were tested for their ability to prevent MPP super(+)-mediated cytotoxicity in human derived SK-N-SH and rat derived MES 23.5 cells. All three HDACIs at least partially prevented MPP super(+)-mediated apoptotic cell death. The protective effects of these HDACIs coincided with significant increases in histone acetylation. These results suggest that HDACIs may be potentially neuroprotective against ABABABcell death and should be explored further in animal models of PD.