Evidence is accumulating suggesting that ethanol has a biphasic effect on several neurotransmitters in the brain and that interactions between two or more transmitters may contribute to the behavioral response obtained after ethanol administration. In the nigrostriatal complex where the most data have been derived, dopaminergic activity responds in a biphasic manner to ethanol treatment. At low doses, dopaminergic activity is elevated, while at high doses, activity is reduced. After chronic ethanol treatment, pre- and postsynaptic dopaminergic activity is hypoactive. Pharmacological data have suggested the possible involvement of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) in the actions of ethanol on the striatal dopaminergic system. In support of this postulate, striatal high-affinity choline uptake, an index of ACh release, is elevated after high doses of ethanol and after ethanol withdrawal. GABA turnover exhibits a biphasic response to ethanol treatment. At low doses of ethanol, GABA turnover is reduced, while at high doses, turnover is unaffected. These latter effects correlate with known interrelationships of these transmitters in the nigrostriatal complex. The data suggest that an action of ethanol on one transmitter may influence the response of another transmitter to ethanol. To further address the interrelationship of transmitters, a high-performance liquid chromatographic method has been developed to study the activity of several transmitters simultaneously. This approach promises to shed more light on this important area.