We describe a patient with AIDS who presented with an acute encephalitis caused by infection with varicella-zoster virus. The hemorrhagic, necrotizing encephalitis had an unusual MR appearance, with innumerable discrete, small, targetlike lesions in the right cerebral hemisphere, which were coalescent in the posterior temporal, parietal, and occipital regions. Of the several known disease patterns of varicella-zoster viral infection in the CNS, this histopathologic pattern of multifocal leukoencephalitis is rare. It is important to recognize, as effective antiviral drug treatments are available.