The objective of the study was to investigate postictal diffusion tensor imaging (DTI) in focal epilepsy. DTI and statistical parametric mapping (SPM) were used to examine objectively the diffusion properties of the brains of 18 patients with intractable focal epilepsy both postictally and interictally and to compare them with 27 normal controls scanned twice. Three sets of statistical tests were performed on each patient's fractional anisotropy and mean diffusivity data: interictal versus controls, postictal versus controls and a third "difference analysis" to test for significant changes in comparison with the differences noted between the two sets of control scans. Thirteen of the 18 patients (72%) had significant increases in mean diffusivity in the interictal scan. No decreases in mean diffusivity were detected. The difference analysis detected significant relative decreases in mean diffusivity postictally in nine patients (50%). These changes were focal in seven patients. In six of these, the site of the epileptic focus was known and co-localized with the diffusivity change in three. No significant changes in anisotropy were noted between the post- and interictal states. The postictal decrease in diffusivity probably reflects cellular swelling in the area of seizure onset and possibly areas of seizure spread. Postictal diffusivity changes appear complex and dynamic and timing after the seizure may be critical. Anisotropy measures appear less sensitive to these changes. Further systematic studies are needed and correlation with outcome after epilepsy surgery will determine the role of postictal diffusion measures in the presurgical evaluation of epilepsy patients.