Following unilateral stroke there is significant loss of function in the body side contralateral to the damage and a robust degenerative-regenerative cascade of events in both hemispheres. It is natural to compensate for loss of function by relying more on the less-affected body side to accomplish everyday living tasks (e.g. brushing teeth, drinking coffee). This is accompanied by a “learned disuse” of the impaired side thought to occur due to repeated experience with its ineptness. However, as investigated in these studies, it may also be due to brain changes instigated by experience with the intact body side. The central hypothesis of these dissertation studies is that experience with the intact forelimb, after unilateral sensorimotor cortex (SMC) damage, disrupts functional recovery with the impaired forelimb and interferes with peri-lesion neural plasticity. Following unilateral ischemic lesions, rats were trained on a skilled reaching task with their intact (less-affected) forelimb or received control procedures. The impaired forelimb was then trained and tested on the same skilled reaching task. Intact forelimb experience worsened performance with the impaired forelimb even when initiated at a more delayed time point following lesions. Intact forelimb training also reduced peri-lesion expression of FosB/ΔFosB, a marker of neuronal activation, and caudal forelimb motor map areas compared to animals without intact forelimb training. It was further established that it is focused training of the intact forelimb and not experience with this limb per se, as animals trained with both forelimbs in an alternating fashion did not exhibit this effect. Transections of the corpus callosum blocked the maladaptive effect of intact forelimb experience on impaired forelimb recovery, suggesting a disruptive influence of the intact hemisphere onto the lesion hemisphere that is mediated by experience. Together these dissertation studies provide insight into how experience with the less-affected, intact body side, can influence peri-lesion neural plasticity and recovery of function with the impaired forelimb. The findings from these studies suggest that compensatory use of the less-affected (intact) body side following unilateral brain damage is not advantageous if the ultimate goal is to improve function in the impaired body side. / text