Research from the present laboratory with adult stroke patients showed that structural neuroplastic changes are correlated with clinical improvements due to constraint-induced movement (CI) therapy. This pilot study evaluated whether comparable changes occur in children receiving CI therapy. Ten children (6 boys) with congenital hemiparesis (mean age: 3 years, 3 months) underwent MRI scans 3 weeks before, immediately before, and immediately after receiving 3 weeks of CI therapy. Longitudinal voxel-based morphometry was performed on MRI scans to determine gray matter change. In addition, the Pediatric Motor Activity Log-Revised was administered at these time points to assess arm use in daily life before and after treatment. Children exhibited large improvements after CI therapy in spontaneous use of the more-affected arm (P < .001, d′ = 3.24). A significant increase in gray matter volume occurred in the sensorimotor cortex contralateral to the more-affected arm (P = .04); there was a trend for these changes to be correlated with motor improvement ( r = 0.63, P = .063). Trends were also observed for increases in gray matter volume in the ipsilateral motor cortex (P = .055) and contralateral hippocampus (P = .1). No significant gray matter change was seen during the 3 weeks before treatment. These findings suggest that CI therapy produces gray matter increases in the developing nervous system and provide additional evidence that CI therapy is associated with structural remodeling of the human brain while producing motor improvement in patients with disabling central nervous system diseases. Copyright © 2013 by the American Academy of Pediatrics.