Background and purpose. Mental practice (MP), which involves cognitive rehearsal of physical movements, is a noninvasive, inexpensive method of enabling repetitive, task-specific practice (RTP). Recent, randomized controlled data suggest that MP, when combined with an RTP therapy program, increases affected arm use and function significantly more than RTP only. As a next step, this 10-subject case series examined the possibility that cortical plasticity is a mechanism underlying the treatment effect of MP when combined with RTP. Method. Ten chronic stroke patients (mean = 36.7 months) exhibiting stable, moderate motor deficits received 30-minute therapy sessions for their affected arms, occurring 3 days/week for 10 weeks, and emphasizing valued activities of daily living (ADLs). Directly after therapy, subjects received 30-minute MP sessions, which required MP of the ADLs performed during therapy. Behavioral outcomes were blindly evaluated using the Action Research Arm Test (ARAT) and the Fugl-Meyer Assessment (FM). Functional magnetic resonance imaging (fMRI) was administered before and after intervention to assess cortical changes. Results. Before intervention, subjects exhibited stable motor deficits. After intervention, subjects exhibited ARAT and FM score increases (+5.3 and +4.2, respectively) and clinically significant gains in ADLs. Postintervention fMRI revealed significant increases in activation to wrist flexion and extension of the affected hand in the premotor area and primary motor cortex ipsilateral and contralateral to the affected hand, as well as in superior parietal cortex ipsilateral to the affected hand. Decreased activation was noted in parietal cortex of the hemisphere ipsilateral to the affected hand. These changes correlated with anatomical regions in which behavioral changes were observed in the ARAT and FM. Conclusions. MP is an easy to use, cost-effective strategy that was again shown to improve affected arm outcomes after stroke. This is the first study to demonstrate alteration in the cortical map in response to MP training.