A child with perinatally acquired HIV infection presented with acute neurologic deterioration. A cerebellar white matter lesion seen on CT and MRI later proved to be progressive multifocal leukoencephalopathy (PML) by histology. Although a recognized disease of HIV-infected adults, PML is certain to be seen with more frequency in HIV-infected children who are surviving longer as a result of improved medical care. Recognition of the clinical and radiographic manifestations is important because of the dismal prognosis.