Five patients with Rasmussen's syndrome (sometimes known as smouldering encephalitis), are presented. This rare form of childhood epilepsy is characterized by intractable partial seizures with progressive neurological and mental impairment. Diagnostic brain biopsy shows the histological changes of active encephalitis, consistent with a viral infection. Although the raised cerebrospinal fluid (CSF) complement and interferon levels seen in some patients support this hypothesis, no infective agent has yet been isolated. All five patients were investigated by transmission computed tomography (CT) of the head, electroencephalography (EEG) and cerebral single-photon-emission computed tomography (SPECT) using 99Tcm-hexamethylpropylenamine oxime (HMPAO) and in addition 123I-amphetamine (IMP) in Patient 1. 99Tcm-HMPAO is now regarded as reflecting cerebral perfusion, whereas the uptake of 123I-amphetamine is more dependent on cell function. In all patients SPECT imaging demonstrated an area of hypoperfusion/hypometabolism which corresponded to the anatomical localization of the epiletogenic foci found by clinical assessment, EEG and CT. In all cases the SPECT study also demonstrated a more extensive area of abnormality than CT, and in the two patients who had sequential studies, alteration in the size of the defect was found which correlated with the patients' changing clinical condition. SPECT imaging in Rasmussen's syndrome may facilitate anatomical localization of the area of pathology, and may demonstrate a changing pattern in cerebral hypoperfusion/hypometabolism. It could also serve as a guide to accurate brain biopsy.