The neurochemical heterogeneity of the rat striatum was assessed in vivo by measuring subregional changes in extracellular dopamine and DOPAC by in vivo electrochemistry and microdialysis in response to amphetamine and the D2 antagonist, (-)-sulpiride. Both in vivo electrochemical and microdialysis experiments indicated a significant rostrocaudal gradient in dopamine release following amphetamine. The increase in dopamine release was highest in the rostral areas (over 800% of baseline values) and lowest in the most caudal subregion (425% of baseline). No lateromedial differences in dopamine release were observed. DOPAC levels decreased in dialysates but were similar for all 6 subregions examined. In contrast, D2 blockade with (-)-sulpiride revealed a lateromedial gradient in the increases seen for dopamine and DOPAC such that greater increases were observed in the lateral subregions. (-)-Sulpiride did not produce any differential effects along the rostrocaudal axis. The regional gradients detected in extracellular fluid changes of dopamine and DOPAC indicate that dopamine release is locally regulated by an interaction between the density of dopaminergic innervation to a particular subregion and the D2 receptor density.