Prefrontal cortical modulation of caudate nucleus dopamine release was investigated in the rhesus monkey using the in vivo microdialysis technique. Reliable and stable basal caudate nucleus dopamine levels were quickly attained within hours following insertion of the dialysis probes. High-potassium (60 mM) or tetrodotoxin (10 microM) infusions significantly altered caudate nucleus dopamine levels in the dialysate indicating that measured dopamine levels reflected impulse-dependent release from the presynaptic pool. Pharmacological augmentation of monoaminergic transmission in the sulcus principalis region of the prefrontal cortex resulted in significant alterations in caudate nucleus dopamine levels. Increase of monoaminergic activity by infusion of either D-amphetamine (100 microM) or cocaine hydrochloride (100 microM) resulted in a gradual and prolonged decrease in caudate nucleus dopamine levels. Similar decreases were noticed in caudate nucleus dopamine metabolite levels. The present results indicate that in non-human primates modulation of dorsolateral prefrontal cortical monoaminergic transmission results in alterations in dopamine levels in subcortical structures. This observation may have clinical implications for therapeutic management of certain neuropsychiatric disorders, particularly schizophrenia.