Several experiments have shown that the dopamine (DA) receptors in the nucleus accumbens control the intensity of locomotor activity; however, there are several contradictory results concerning the role of the accumbens in the regulation of the direction of locomotion. To further evaluate the contribution of dopaminergic function in the accumbens to the direction of locomotion, we first compared the effect on the direction of locomotor activity of unilateral intra-accumbens injections of the nonspecific DA antagonist haloperidol, the specific D-1 antagonist SCH-23390, the specific D-2 antagonist metoclopramide. In the second part of the experiment, we examined the effect on the direction of locomotor activity of unilateral intra-accumbens injections of the non-specific DA agonist apomorphine, the specific D-1 agonist SKF-38393, the specific D-2 agonist LY-171555, and the combination of SKF-38393 and LY-171555. Haloperidol, metoclopramide and to a lesser extent, SCH-23393 together with peripheral amphetamine injections produced a locomotor bias that resulted in ipsilateral turning. Apomorphine, LY-171555 or the combination of SKF-38393 and LY-171555 (but not SKF-38393 alone) produced a locomotor bias that resulted in contralateral turning. No significant locomotor bias was produced by intra-accumbens injection of the various vehicles. These results suggest that the bilateral DA organization thought to exist in the nigro-striatal pathway for the control of locomotion may also be true for the mesolimbic dopamine system.