Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT) and dopamine (DA) pathways in regulating the alcohol intake of rats selectively bred for their high alcohol seeking behavior (P and HAD lines). Neurochemical data indicate that high alcohol seeking behavior (when compared with data from rats with low alcohol seeking characteristics) is associated with (a) lower contents of 5-HT in certain limbic regions, e.g., n. accumbens (Acb), frontal cortex, (b) a lower content of DA in the Acb, and (c) higher densities of 5-HT1A receptors in certain limbic regions, e.g., cerebral cortex. Neurochemical data also suggest that ethanol can activate the DA and 5-HT systems projecting to the Acb. Neuropharmacological studies demonstrated that local microinfusion of a 5-HT agonist into the Acb of the P line of rats enhanced ethanol drinking. Intracranial self-administration studies established that P rats will self-administer ethanol directly into the ventral tegmental area (VTA). Overall the data suggest the involvement of certain VTA DA and dorsal raphe nucleus 5-HT pathways in regulating high alcohol drinking behavior.