Neuronal activity was recorded from the neostriatum of freely moving rats at least 1 week following either sham or bilateral ablations of frontal and somatosensory cortex. In both groups of animals, the majority of neurons increased firing rat in close temporal association with spontaneous movement. No group differences emerged either with respect to baseline firing rates or open-field behavior. Following amphetamine administration, however, the excitatory response of motor-related neurons was suppressed in cortical-lesioned rats. A behavioral clamping procedure, which assessed neuronal activity during matched pre- and post-amphetamine behaviors, confirmed these results, suggesting that the amphetamine-induced changes in neuronal activity reflect a direct drug effect independent of behavioral feedback. In animals that received a subsequent injection of 1.0 mg/kg haloperidol, cortical lesions attenuated the ability of this neuroleptic to block both the behavioral and neuronal effects of amphetamine. Collectively, these results support mounting evidence for an important modulatory influence of cortical afferents on the amphetamine-induced excitation of neostriatal neurons and the reversal of this effect by haloperidol.