To assess motor cortex plasticity after constraint-induced movement therapy in patients with ischemic perinatal stroke, functional MRI and transcranial magnetic stimulation were applied. Seven hemiparetic patients with ischemic perinatal stroke of the middle cerebral artery and preserved crossed corticospinal projections to the paretic hand were studied before and after 12 days of constraint-induced movement therapy. After therapy, all patients demonstrated improved manual motor function. Transcranial magnetic stimulation of the motor cortex of the affected hemisphere revealed a significant increase of motor-evoked potential amplitude recorded from the paretic hand, whereas no significant change was detected in the nonparetic hand after transcranial magnetic stimulation of the contralesional hemisphere. Functional MRI revealed increased activation of the contralateral central region (including primary sensorimotor cortex) and supplementary motor area during active movement of the paretic hand. No change in functional MRI activation was detected during passive movement of the paretic hand or during active and passive movement of the nonparetic hand. In ischemic perinatal stroke with crossed corticospinal projections, constraint-induced movement therapy induces neuroplastic changes on the synaptic level, detected as increased excitability (transcranial magnetic stimulation) and increased task-related brain activation (functional MRI) in the primary motor cortex of the lesioned hemisphere.