In this functional magnetic resonance imaging (fMRI) study, we examined changes--relative to healthy controls--in the cortical activation and connectivity patterns of two patients who had undergone unilateral heterotopic hand replantation. The study involved the patients and a group of control subjects performing visually paced hand movements with their left, right, or both hands. Changes of effective connectivity among a bilateral network of core motor regions comprising M1, lateral premotor cortex (PMC), and the supplementary motor area (SMA) were assessed using dynamic causal modelling. Both patients showed inhibition of ipsilateral PMC and SMA when moving the healthy hand, potentially indicating a suppression of inference with physiological motor execution by the hemisphere controlling the replanted hand. Moving the replanted hand, both patients showed increased activation of contralateral PMC, most likely reflecting the increased effort involved, and a pathological inhibition of the ipsilateral on the active contralateral M1 indicative of an unsuccessful modulation of the inhibitory M1-M1 balance. In one patient, M1 contralateral to the replanted hand experienced increased tonic (intrinsic connectivity) and phasic (replanted hand movement) facilitating input, whereas in the other, pathological suppression was present. These differences in effective connectivity correlated with decreased behavioural performance of the latter as assessed by kinematic analysis, and seemed to be related to earlier and more intense rehabilitative exercise commenced by the former. This study hence demonstrates the potential of functional neuroimaging to monitor plastic changes of cortical connectivity due to peripheral damage and recovery in individual patients, which may prove to be a valuable tool in understanding, evaluating and enhancing motor rehabilitation.