This is the first report on 201thallium-single photon emission computed tomography (201Tl-SPECT) brain scan of a patient with herpes simplex encephalitis (HSE). The presented 201Tl-SPECT observations are correlated with 99mtechnetium hexamethylpropylene amine oxime (99mTc-HMPAO) perfusion SPECT and magnetic resonance imaging (MRI) findings. Brain 99mTc-HMPAO perfusion SPECT reveals a hyperperfusion in the right temporal lobe with extension to the parietal lobe and a hypoperfusion in the ipsilateral occipital lobe. 201Tl-SPECT shows a fixation in the right temporal lobe coinciding with the gadolinium enhancement on MRI. The right occipital lesion shown by gadolinium captation on MRI and hypoperfusion on 99mTc-HMPAO perfusion SPECT was not evident on the 201Tl SPECT. These findings could illustrate that the lesions might be different pathophysiologically.