Long-term ethanol use and long-term tobacco use frequently occur together, which suggests concurrent dependence on ethanol and nicotine. Consequences of this form of polydrug dependence are not well understood, however. Previous evidence suggests detrimental effects of long-term ethanol and beneficial effects of nicotine exposure on neuronal viability. Thus, the present study was designed to use an organotypic hippocampal slice culture model to examine the ability of chronic and acute nicotine exposure to reduce neurotoxicity associated with withdrawal from long-term ethanol exposure.