Stimulation of the nigro-neostriatal dopamine pathway results in an accumulation of both free and conjugated dihydroxy-phenylacetic acid (DOPAC) in the rat neostriatum. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce predictable changes in the levels of both free and conjugated DOPAC in both the neostriatum and, in most cases, in the frontal cortex. Drugs such as the antipsychotics which increase impulse flow in the nigro-neostriatal dopamine neurons increase both free and conjugated DOPAC levels in both the neostriatum and frontal cortex. Drugs which reduce impulse flow, such as d-amphetamine and apomorphine, cause a reduction in free DOPAC in both the neostriatum and frontal cortex but reduce DOPAC conjugate only in the neostriatum. Pargyline, a monoamine oxidase inhibitor, causes an extensive depletion of free and conjugated DOPAC in both the striatum and frontal cortex, indicating that these metabolites are rapidly cleared from both of these brain areas.