Studies of in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) have reported reductions in both functional and structural connectivity between hippocampal structures and adjacent brain regions. However, little is known about the connectivity among the default mode network (DMN) in mTLE. Here, we hypothesized that both functional and structural connectivity within the DMN were disturbed in mTLE. To test this hypothesis, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were applied to examine the DMN connectivity of 20 mTLE patients, and 20 gender- and age-matched healthy controls. Combining these two techniques, we explored the changes in functional (temporal correlation coefficient derived from fMRI) and structural (path length and connection density derived from DTI tractography) connectivity of the DMN. Compared to the controls, we found that both functional and structural connectivity were significantly decreased between the posterior cingulate cortex (PCC)/precuneus (PCUN) and bilateral mesial temporal lobes (mTLs) in patients. No significant between-group difference was found between the PCC/PCUN and medial prefrontal cortex (mPFC). In addition, functional connectivity was found to be correlated with structural connectivity in two pairwise regions, namely between the PCC/PCUN and bilateral mTLs, respectively. Our results suggest that the decreased functional connectivity within the DMN in mTLE may be a consequence of the decreased connection density underpinning the degeneration of structural connectivity. Hum Brain Mapp, 2010. (c) 2010 Wiley-Liss, Inc.