Diffusion-weighted imaging (DWI) has been employed in many brain pathologies, but with few studies only and heterogeneous results in herpes simplex virus encephalitis (HSVE). Diffusion tensor imaging (DTI) in comparison to DWI yields additional directional diffusion data, adding information and enabling a more differentiated description of brain pathologies. The authors addressed the question whether tissue changes as identified on T2-weighted magnetic resonance imaging (MRI) could be further characterized by DTI, in particular whether different forms of edema may occur in HSVE. Six patients with HSVE confirmed by positive polymerase chain reaction (PCR) from cerebrospinal fluid (CSF) samples were studied. Patients were examined with MRI including DTI in the early stage of the infection. Conventional MRI- and DTI-derived parameter maps were analyzed for signal change qualitatively and by region-of-interest (ROI) analysis of the affected brain parenchyma. All patients showed typical clinical characteristics of HSVE and lesions in the mediobasal temporal structures and insula. In two cases hemorrhagic inflammatory tissue changes were found. DTI analysis showed slightly reduced mean diffusivity (MD) and increased fractional anisotropy (FA) values in the earliest phase. Patients scanned at day 14 or later had lesions with increased MD and reduced FA in accordance with inflammatory vasogenic edema. This study confirms signal change consistent with the presence of inflammatory vasogenic edema in HSVE as the most prominent DTI finding. In the early stage slight reductions of MD may be found, which might be due to a specific mechanism of viral infection.