Deafferentation such as the amputation of a body part causes cortical reorganization in the primary motor cortex (M1). We investigated whether this reorganization is reversible after reconstruction of the lost body part. We tested two patients who had long-standing thumb amputations followed by thumb reconstruction with toe-to-thumb transfer 9 to 10 mo later and one patient who underwent thumb replantation immediately following traumatic amputation. Using transcranial magnetic stimulation, we measured the motor evoked potential (MEP) threshold, latency, short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) at different time points in the course of recovery in abductor pollicis brevis muscle. For the two patients who underwent late toe-to-thumb transfer, the rest motor threshold was lower on the injured side than that on the intact side before surgery and it increased with time after reconstruction, whereas the active motor threshold remained unchanged. The rest and active MEP latencies were similar on the injured side before and < or =15 wk after surgery and followed by restoration of expected latency differences. SICI was reduced before surgery and progressively normalized with the time after surgery. ICF did not change with time. These physiological measures correlated with the recovery of motor and sensory functions. All the measurements on the intact side of the toe-to-thumb transfer patients and in the patient with thumb replantation immediately following traumatic amputation remained stable over time. We conclude that chronic reorganization occurring in the M1 after amputation can be reversed by reconstruction of the lost body part.