OBJECTIVE: To determine whether cortical changes occur following participation in a program of modified constraint-induced movement therapy (mCIMT). DESIGN: Pre-post, case series. SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Two men and 2 women with unilateral stroke occurring more than 1 year prior to study entry and moderate stable motor deficits. INTERVENTION: Subjects participated in mCIMT, comprised of structured, 30-minute therapy sessions emphasizing affected arm use in valued activities, which occurred 3 days a week for 10 weeks. Their unaffected arms were restrained 5 days a week for 5 hours. MAIN OUTCOME MEASURES: The Action Research Arm Test (ARAT), upper-extremity portion of the Fugl-Meyer Assessment (FMA), Motor Activity Log (MAL), and functional magnetic resonance imaging (fMRI) at 4T were administered before and after mCIMT. RESULTS: Three subjects exhibited score increases on the MAL, ARAT, and FMA, representing increased affected arm use, impairment, and function. These subjects reported new ability to perform valued activities with the affected hand, such as writing. These subjects also displayed cortical reorganization on fMRI. One subject exhibited minimal affected arm use changes, modest function changes, and no cortical fMRI changes. CONCLUSIONS: Increased affected arm use during mCIMT appears to induce cortical reorganization, as measured by fMRI. In patients who responded to mCIMT, cortical reorganization was positively related to degree of increase in affected arm use and ability. Because mCIMT is more easily administered than longer duration protocols, mCIMT may be a more practicable way of studying plasticity.