<p>Stroke patients with apraxia typically have difficulty imitating simple postures and movements done by the examiner and tasks that demand pantomime of daily actions with tools. We used voxel-based lesion-symptom mapping (VLSM) to explore the impact of stroke lesion topography on imitation and pantomime following left (<i>n</i> = 40) and right (<i>n</i> = 38) hemispheric damage (LHD, RHD). In LHD, damage to association and projection tracts and the inferior parietal cortex impaired imitation and pantomime, while damage to the insular cortex selectively impaired imitation. In RHD, damage to association and projection tracts, supplementary motor area and insula, impaired both skills. Damage to sensory-motor, inferior parietal, opercular and cingulate cortices selectively impaired pantomime, and damage to the external capsule and putamen selectively impaired imitation. Conjunction analysis was dominated, in both hemispheres, by voxel clusters related in a selective manner to either pantomime or imitation. VLSM results for pantomime in LHD and imitation in RHD are tentative, being based on a lenient criterion, while the results of imitation in LHD and pantomime in RHD are robust. Overall, the results suggest that imitation and pantomime involve largely separate parts of the praxis network, with marked differences in the functional organization of these motor skills in the two hemispheres.</p>