Primary motor cortex (M1) excitability is modulated by both ipsilateral limb movement and passive observation of movement of the contralateral limb. An interaction of these effects within M1 may account for recent research suggesting improved functional recovery of the impaired arm following stroke by viewing a mirror reflection of movements of the unimpaired arm superimposed over the (unseen) impaired arm. This hypothesis was tested in the present study using single-pulse transcranial magnetic stimulation (TMS) in eight neurologically healthy subjects. Excitability of M1 ipsilateral to a phasic, unilateral hand movement was measured while subjects performed paced (1 Hz), unilateral index finger-thumb opposition movements. Motor evoked potentials (MEPs) were obtained from the inactive first dorsal interosseous (FDI) in each of four viewing conditions: Active (viewing the active hand), Central (viewing a mark positioned between hands), Inactive (viewing the inactive hand) and Mirror (viewing a mirror-reflection of the active hand in a mirror oriented in the mid-sagittal plane) and with both hands at rest (Rest). MEPs were significantly enhanced during ipsilateral hand movement compared with the Rest condition (P<0.05). Largest MEPs were obtained in the Mirror condition, and this was significant compared with both the Inactive and Central viewing conditions (P<0.05). There was no difference between the dominant and non-dominant hand. Excitability of M1 ipsilateral to a unilateral hand movement is facilitated by viewing a mirror reflection of the moving hand. This finding provides neurophysiological evidence supporting the application of mirror therapy in stroke rehabilitation.