Slow-growing, infiltrative brain tumours may modify the electrophysiological balance between the two hemispheres. To determine whether and how asymmetry in interhemispheric excitability might occur following “wide-awake surgery” for this type of tumour, we recorded electroencephalograms during a simple visuo-manual reaction time paradigm performed by five patients between 3 and 12 months after surgery. Interhemispheric excitability asymmetries were computed by comparing the amplitudes of event-related potentials (ERPs) in the injured hemisphere to those in the healthy hemisphere. For the two patients with the smallest lesions (7.1 and 11.5 cm3, respectively), increased excitability within the ipsilesional hemisphere was evidenced by characteristics increases in the ERP amplitude at several sites, with few occurrences in the contralesional hemisphere. For smaller lesions (and under certain experimental conditions), cortical excitability in the injured hemisphere may increase in order to maintain local compensation. In addition, we observed and increased excitability in the contralesional frontal homologue for one patient who underwent an extensive resection. Post-operative monitoring of interhemispheric asymmetries in ERP amplitudes is of value for determining task constraints inducing electrophysiological imbalance and guiding rehabilitation.