The most commonly abused drugs, alcohol and nicotine, are likely also the most costly drugs in terms of health and societal costs. A large body of evidence from epidemiological studies indicate that smoking and alcohol-intake are positively correlated. The mesocorticolimbic dopamine system has been implicated in mediating some of the reinforcing effects of ethanol, however, the mechanism(s) of action remains to be elucidated; consideration as to ethanol's ability to interact with ligand-gated ion channels should be considered. Accumulating evidence from electrophysiological, pharmacological and neurochemical studies suggest that ethanol may interact with the nicotinic acetylcholine receptor (nAChR). Thus, it has been shown that the ethanol-induced stimulation of the mesolimbic dopamine system and of locomotor activity as well as ethanol intake and preference in rodents may involve central nicotinic acetylcholine receptors. Additionally, data has been presented that nAChRs located in the ventral tegmental area may be of particular importance for these effects of ethanol. Studies aimed at defining the nAChR subpopulation(s) involved in mediating ethanol-induced locomotor stimulation and accumbal dopamine overflow as well as ethanol-intake have revealed that alpha(3)beta(2) or alpha(6) (using alpha-Conotoxin MII) but not alpha(4)beta(2) (using dihydro-beta-erythroidine) or alpha(7) (using methyllycaconitine), could represent targets for developing new drugs in the treatment of alcoholism. These results do not allow any conclusion as to whether the involvement nAChRs in mediating the effects of ethanol is direct and/or indirect. With regard to an indirect effect, evidence has accumulated indicating that the cholinergic excitatory input to the dopaminergic neurons in the ventral tegmental area may be an important part of the neuronal circuits mediating natural as well as drug-rewarded behavior. The possibility may thus be considered that ethanol activates the cholinergic afferents causing a release of acetylcholine in the ventral tegemental area leading to a stimulation of nAChRs and thereby excite the mesocorticolimbic dopamine system.