Movement asymmetry in humans and animals is often considered as being induced by the brain lateralization of the motor system. In the present work, the hemispheric asymmetry for motor planning as a cause of behavioral lateralization was examined. This study was carried out on normal volunteers and patients suffering unilateral brain damage caused by a stroke. Motor planning was evaluated by using the motor imagery of hand movement, a mental representation of a motor pattern that includes its internal simulation but not its real execution. The present study shows marked similarities between virtual movement executed during motor imagery and real movements. Thus, performance time showed a high correlation between real and virtual movements in the following conditions: (1) during dominant and non-dominant hand movements; (2) in simple and complex motor tasks; (3) in young control subjects; (4) in stroke patients; and (5) control subjects aged-matched to stroke patients. Brain strokes increased the performance time in both real and virtual movements. Left-brain strokes decreased the velocity of the real movements in both hands, whereas right-brain strokes mainly disturbed movements in the left hand. A similar effect was observed for virtual movements, suggesting a left-brain dominance for motor planning in humans. However, two-handed movement tasks suggest a complex interaction during motor planning, an interaction that facilitates motor performance during mirror movements and delays motor execution during non-mirror movements.