This is a case of herpes simplex encephalitis (HSE) examined with Tc-99m-ethyl cysteinate dimer (ECD) and Tc-99m-hexamethyl propyleneamine oxime (HMPAO) SPECT. Static images obtained with Tc-99m-ECD showed a reduced tracer uptake of the temporal lobe but focal hyperactivity using Tc-99m-HMPAO. Dynamic images indicated regional increase of cerebral blood perfusion with both tracers. Technetium-99m-ECD had rapid washout from the inflammed tissue, while Tc-99m-HMPAO had avid uptake. Hypofixation of Tc-99m-ECD leads to failure to detect the characteristic finding of temporal robe hyperemia in acute HSE.