OBJECTIVE: In temporal lobe epilepsy (TLE), frontal-temporal connections are integral parts of the epileptogenic network. Although frontal-temporal gray matter abnormalities have been consistently demonstrated in TLE, white matter connections between these two lobes require further study in this disease setting. We therefore investigated the integrity of two major frontal-temporal white matter association tracts, uncinate fasciculus (UF) and arcuate fasciculus (AF), and their clinical correlates. METHODS: Using diffusion tensor imaging (DTI) tractography, integrity of the UF and AF was examined in 22 individuals (12 subjects with TLE and 10 age-matched healthy controls). DTI indices of these tracts were compared between the two subject groups and correlates examined with clinical variables that included age of seizure onset, duration of epilepsy, history of febrile seizure and antiepileptic medication exposure. RESULTS: In subjects with TLE, the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of UF and AF ipsilateral to the side of seizure onset were abnormal when compared to healthy controls. Furthermore, lower UF FA correlated with earlier age of seizure onset. CONCLUSION: TLE is associated with abnormal integrity of frontal-temporal white matter tracts, but only on the side of seizure onset. This suggests that frontal-temporal white matter tracts are vulnerable to recurrent seizures and/or the factors precipitating the epilepsy.