Mirror focus (MF) is a cortical epileptogenic lesion that is posited to develop in the contralateral site to a cortical primary focus (PF) by secondary epileptogenic mechanisms. Previous animal evidence supports the implication of gamma-aminobutyric acid (GABA) in this phenomenon, but this contention has not yet been substantiated by clinical findings. Here we report for the first time clinical evidence suggesting the involvement of GABAergic cortical transmission in MF pathogenesis, in a 37-year-old man affected by a lesional PF in the right frontal lobe and a homotopic MF in the contralateral hemisphere, triggered by hyperventilation. One year after surgical excision of the PF, the electric activity of the MF remained unchanged, but was accompanied by a significant increase in the density of GABA(A)/benzodiazepine receptor binding in the left frontal lobe, as measured by (123)I-Iomazenil SPECT. These results extend previous evidence on the involvement of GABAergic signaling in MF pathophysiology.