Results of a magnetoencephalography (MEG) brain imaging study conducted to examine the cortical responses during action execution and action observation in 10 healthy adults and 8 age-matched adults with Down syndrome are reported. During execution, the motor responses were strongly lateralized on the ipsilateral rather than the contralateral side in the Down syndrome group. Observation of movement activated a network of cortical regions that was similar to the control group; however, there was no significant peak activity in the motor areas. In addition, the overall pattern of neural activation was more scattered and less organized in the Down syndrome group. These results further support the hypothesis of a dysfunction in the execution/observation matching system in adults with Down syndrome.