Herpes simplex virus encephalitis (HSVE) typically affects the baso-temporal brain. The venous blood drainage of this region mainly occurs via the basal vein of Rosenthal (BVR), which can easily be monitored by transcranial color-coded duplex sonography (TCCS), and might be a useful parameter for the activity of the disease. Serial blood flow velocity (BFV) measurements of the BVR and the basal cerebral arteries were performed in five acute HSVE patients by means of transcranial color-coded duplex sonography (TCCS). Remarkable increased BFV of the BVR at the affected side was found in all patients, showing a maximum within the first 8 d of infection followed by a tendency toward normalisation during the next weeks. In comparison, changes of BFV in the basal cerebral arteries were much more heterogeneous. Our findings suggest that TCCS measurements of the BVR might be used as an additional diagnostic bed-side tool to evaluate patients with HSVE during the acute stage.