Recent investigations of the function of the strionigral pathway have utilized the intranigral injection of gamma-aminobutyric acid (GABA) agonist and antagonist drugs. While the unilateral application of these substances typically produces rotational behavior, the direction of this turning (ipsilateral or contralateral to the injected hemisphere) differs in several reports. The present study determines whether the direction of this drug-induced turning depends upon the locus of migral stimulation. Picrotoxin and bicuculline methiodide were injected into either the pars compacta or the pars reticulata of the substantia nigra at several anterior-posterior levels. Injection of these drugs into the pars compacta resulted in ipsilateral turning while injection into the pars reticulata produced contralateral rotation. Both of these effects were dose-dependent and were elicited by similar threshold doses of picrotoxin. Prior 6-hydroxydopamine treatment abolished the ipsilateral but not the contralateral rotation. In contrast, muscimol injections produced contralateral turning independent of whether they were made into the pars compacta or pars reticulata. However, 6-hydroxydopamine treatment only attenuated the contralateral turning produced by pars compacta injections. These findings provide a histological basis for understanding the different types of turning behavior elicited by the intranigral injection of GABA agonists and antagonists. In addition, they suggest that GABA receptors mediate at least two independent actions in substantia nigra.