It is unclear whether focal epilepsies chronically influence the processing of cortex distant to the epileptogenic zone. Therefore, motor cortex excitability was analysed in patients with temporal and extratemporal epilepsies whose epileptogenic zones did not include the primary motor area. Single and paired-pulse transcranial magnetic stimulation (TMS) was applied to the primary motor cortex in 20 healthy controls and 23 patients with focal epilepsy (39.4 +/- 13.2 years; 12 left, 11 right; 14 temporal, nine extratemporal: six frontal, three parieto-occipital) ipsi- and contralateral to the epileptogenic zone. In all patients, the epileptogenic zone did not include the primary motor cortex. The resting motor threshold (RMT), the cortical silent period (CSP), the intracortical inhibition [ICI; combined interstimulus intervals (ISI) 2 and 3 ms] and the intracortical facilitation (ICF; combined ISI 10 and 15 ms) were determined. The measures obtained ipsilateral to the epileptogenic zone were compared with those elicited in contralateral hemispheres and, in exploratory analyses, with controls using non-parametric tests, including Hodges-Lehmann estimates of median differences (HLE) with 95% confidence intervals (CI). In the patient group, the CSP elicited in the ipsilateral motor cortex (median 162.3 ms) was shortened compared with the contralateral CSP (median 174.6 ms; HLE 15.9 ms; CI 6.2, 27.0 ms; P = 0.002). This interhemispheric difference was more pronounced in extratemporal epilepsies (HLE 23.4 ms; CI -3.2, 67.6 ms) compared with temporal epilepsies (HLE 14.3 ms; CI 4.7, 26.2 ms). Patients with parieto-occipital epilepsies showed the greatest interhemispheric differences in CSP (HLE 33.5 ms) and patients with mesial temporal epilepsies the smallest (HLE 9.9 ms). No significant differences were found between ipsi- and contralateral RMT, ICI or ICF. In analyses of subgroups, the CSP was shorter in epileptic hemispheres of patients with extratemporal epilepsies (141.4 ms) than in controls (173.4 ms; HLE 40.0 ms; CI 3.2, 83.4 ms; P = 0.029). ICF was increased in epileptic hemispheres of extratemporal epilepsies (147.6%) compared with temporal epilepsies (114.6%; HLE 33.0%; CI 4.1, 68.3%; P = 0.038). The results suggest that focal epilepsies influence chronically distant cortex, leading to decreased inhibition and increased facilitation in the ipsilateral motor cortex even when the epileptogenic zone is apart from it. This alteration may be due to synaptic reorganization and appears to be more pronounced in extratemporal and neocortical temporal than in mesial temporal epilepsies. This may have diagnostic implications.