To study the connections between bilateral mesial frontal (MF) regions. We evaluated synchrony of spikes, recorded by subdural electrodes, arising from bilateral MF regions using cross correlation in MF epilepsy. A seven-year-old boy with intractable daily bilateral asymmetric tonic seizures and a normal MRI was investigated. To confirm the lateralization of epileptogenicity, subdural electrodes were implanted bilaterally. Only spikes of an amplitude of 400 μV or more were analyzed. Of 92.4% (194/210) of the left MF spikes recorded for 30 minutes, an approximately synchronous spike was also detected in the right MF region. Cross correlation analysis demonstrated that for 88.7% of the bilateral MF spikes (172/194, 88.7%) the left MF spike led the contralateral spikes with relative fixed peak-to-peak intervals (18.9 ± 11.1 ms) and high cross correlation values (0.81 ± 0.10). An estimated conduction velocity of 7.2 ± 9.8 m/sec was calculated (assuming no synaptic delay). After a second period of more extended invasive EEG monitoring, a left partial frontal lobectomy was performed and the patient immediately had a few brief seizures before remaining seizure-free for a follow-up period of 14 months. We conclude that the propagation of spikes between bilateral MF regions most likely occurs mainly through myelinated callosal fibres. In addition, this cross correlation method showed that the left MF spikes, most of the time, preceded the right MF spikes suggesting that the epileptogenic zone was localized in the left MF region.