Changes of motor cortex organization after lesions in the nervous system can be demonstrated by mapping the motor cortex with transcranial magnetic stimulation. We studied cortical plasticity in 22 patients who had a unilateral immobilization of the ankle joint without peripheral nerve lesion. The motor cortex area of the inactivated tibial anterior muscle diminished compared to the unaffected leg without changes in spinal excitability or motor threshold. The area reduction was correlated to the duration of immobilization. It could be quickly reversed by voluntary muscle contraction. This indicates a functional (and not morphological) origin of the phenomenon.