The experiments examined the suggestion that the dopaminergic (DA) projection to the motor cortex are involved in the motor impairments that follow complete hemitelencephalic DA depletions. The neurotoxin, 6-hydroxydopamine (6-OHDA), was injected unilaterally into the sensorimotor cortex (MCtx), the ventral tegmental area (VTA), or into the substantia nigra pars compacta (SN) of rats trained to reach for food with either forelimb. The SN injections produced large (greater than 95%) unilateral striatal dopamine (DA) depletions and severe bilateral impairments in limb use. VTA and MCtx injections did not produce impairments in limb use or severe depletions of cortical DA. An effective test of the contribution of cortical DA to skilled limb use must await a more effective technique for producing selective cortical DA depletion. Nevertheless, the results suggest that the severe impairments of skilled forelimb use that follow hemitelencephalic DA depletions may stem primarily from depletion of the nigrostriatal DA projection.