We have previously shown that early forced overuse of the affected forelimb worsens outcome following moderately severe transient focal cortical ischemic stroke in rats using a distal middle cerebral artery occlusion (MCAo) model. This effect may be site-dependent, because we have also found that early forced use of the affected limb after unilateral 6-OHDA induced degeneration of ascending nigrostriatal dopamine neurons markedly enhanced functional outcome and is neuroprotective. The present study examines the effects of early overuse and disuse following a moderately severe proximal MCAo model, by means of intraluminal suture occlusion. Ischemia was produced in male Long-Evans rats with 60 min of occlusion, or sham surgery was performed. Early overuse or disuse of the affected forelimb was forced by immobilizing either the ipsilateral or contralateral forelimb, respectively, in a plaster cast or the animal was left uncasted. Casts were removed on day 10 and sensorimotor testing was performed weekly during days 17-38. Animals were sacrificed on day 45 and brains were fixed for later cresyl violet staining. The MCAo+contralateral cast group performed worse than all other groups on tests of forelimb sensorimotor function. All MCAo groups regardless of cast condition had significant atrophy of the ischemic striatum, but there was no significant atrophy of the ischemic cortex in any group. Forced disuse, but not overuse, of the affected forelimb immediately following proximal ischemia using the intraluminal suture model has detrimental effects on functional outcome, without exaggerating anatomical damage. The effects of disuse and overuse during the first 10 days after stroke differ depending on cortical or subcortical involvement.