Using both the RIA and HPLC-EC methods, we studied the effect of intrastriatal injection of bicuculline (Bic), a GABA antagonist as well as the intranigral injection of [D-Arg1, D-phe5, D-Trp7-9, Leu11] substance P, the SP antagonist on the metabolism of dopamine (DA) at the striatum after the unilateral irreversible occlusion of the right middle cerebral artery (MCAO) of rats. Intrastriatal injection of 80 nmol Bic increased DOPAC level except DA and HVA in the striatum. The increase of striatal DOPAC was statistically significant in the MCAO group as compared with that in the non-ischemic controls. The above effects of intrastriatal Bic on DA and its metabolites were completely reversed with an intranigral injection of 5 nmol of substance P. It is suggested that the effect of intrastriatal Bic on DA metabolites in the striatum is mediated by substance P in the substantia nigra and that the regulatory effect of GABA and SP on striatal DA is working in middle cerebral artery occlusion.