Morphological and pharmacological data suggest the existence of a reciprocal interaction between the mesencephalic dopamine (DA) system and the serotonin (5-HT) system originating in the dorsal raphe nucleus (DRN). In the present work, a DA D2 receptor-mediated regulation of 5-HT extracellular concentrations in the DRN is described, by using brain microdialysis in freely moving rats. Local infusion of the nonselective DA agonist apomorphine produced a dose-dependent increase in the extracellular concentration of 5-HT in the DRN, which was prevented by previous infusion of the specific D2 antagonist raclopride but not of the D1 antagonist SCH-23390. Furthermore, local infusion of the selective D2 agonist LY-171,555 increased extracellular 5-HT levels in the DRN, and this effect was also prevented by the previous infusion of raclopride. It is postulated that DA, either from projections from the substantia nigra or the ventral tegmental area or from the DA-containing neurons of the DRN, may increase 5-HT release in the DRN, which, through autoreceptor stimulation, can profoundly influence the activity of ascending serotoninergic neurons.