In this work, functional changes in the sensorimotor cortex following unilateral hand immobilisation were investigated in 11 healthy volunteers. Sensory and motor function of both hands was also assessed. Cortical activation was monitored with functional magnetic resonance imaging at 3 T. All examinations were performed prior to and directly after 72 h of immobilisation of the dominant hand and wrist. Following unilateral immobilisation, cortical activation increased substantially during tactile stimulation of the non-immobilised hand. This was particularly evident in the ipsilateral somatosensory cortex. Additionally, a redistribution of hemispheric dominance towards zero lateralisation was seen. A bilateral cortical activation increase was also seen during performance of a finger-tapping task by the non-immobilised hand, although this increase was less prominent than during tactile stimulation. In contrast, performance of the finger-tapping task with the immobilised hand resulted in an activation decrease, predominantly in the ipsilateral sensorimotor cortex. This site was anatomically close to the regional activation increase of the non-immobilised hand. These functional changes were associated with reduced grip strength, dexterity and tactile discrimination of the immobilised hand, and simultaneously improved tactile discrimination of the non-immobilised hand. This suggests that brain adaptation following hand immobilisation includes inter-hemispheric dynamics. In summary, the improved sensory function of the non-immobilised hand following unilateral immobilisation is associated with cortical expansion, predominantly contralateral to the immobilised hand, and a redistribution of hemispheric dominance. Both cortical and clinical effects of immobilisation were identified after 72 h, suggesting rapid inter-hemispheric plasticity using existing neural substrates.