OBJECTIVE: It is Important to differentiate human herpesvirus 6 (HHV-6) -associated from herpes simplex encephalitis encephalopathy (HSE). These conditions are like, Although With regard to Involvement of the mesial temporal lobe, HSE is sensitive to acyclovir but HHV-6 encephalopathy is not. We Compared the imaging findings of the two conditions. MATERIALS AND METHODS: We Encountered eight cases of HHV-6 encephalopathy and nine cases of HSE. We divided into an observation time early, middle, and late periods defined as 0-2, 3-30 and more than 30 days from the onset of neurologic symptoms. Differences Between HHV-6 encephalopathy and HSE on CT scans in the early period and in distribution and temporal Changes in the regions AFFECTED on MR images in the three periods Were Analyzed. RESULTS: At MRI in the early and middle periods, all eight Patients With HHV-6 encephalopathy HAD exclusive Involvement of the mesial temporal lobes, and all nine Patients With HSE HAD Involvement of Both the mesial temporal lobes and the extratemporal regions (p <0. 01). Among WHO Patients underwent MRI head, six of six With HHV-6 but none of six encephalopathy With HSE HAD resolution of high signal intensity on T2-weighted and FLAIR images (p <0. 01). Among Patients WHO underwent head CT in the early period, none of the four With HHV-6 encephalopathy and six of the seven With HSE HAD abnormal findings, treats including parenchymal swelling, Decreased attenuation of affected regions, and abnormal gyral enhancement (p <0. 05) . CONCLUSION: Serial MRI Showed abnormal transient signal intensity in the mesial temporal lobes in Patients With HHV-6 encephalopathy but persistent abnormal signal intensity in the mesial temporal lobes Both the extratemporal and regions in Patients With HSE. CT in the early period Showed no abnormality in Patients With HHV-6 encephalopathy but definite abnormal findings in Patients With HSE. These Differences May be useful in the differential diagnosis of the two conditions.