A 43-year-old Caucasian man with AIDS presented with progressive confusion, blurring of vision, and personality change for 6 weeks in March 1999. He was successfully treated for Pneumocystis jiroveci pneumonia 2 months prior to his presentation. He did not have any headaches or seizures. He was afebrile. Examination revealed left cerebellar signs, dysphasia, and clear evidence of left posterior-occipital lesion with right homonymous hemianopia. He was unable to identify simple objects such as a pen or coins nor name colors correctly. He was disoriented in time and place. His CD4 count was 34 cells/mm3. His HIV ribonucleic acid (RNA) level was 800,789 copies/mL. Serum toxoplasma immunoglobulin G antibodies were negative. A magnetic resonance imaging (MRI) scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema (Figure 1). Cerebrospinal fluid (CSF) was clear in color with a polymorph count of three cells and a lymphocyte count of five cells. Gram staining of CSF did not show any organism, and bacterial culture of CSF was negative. CSF toxoplasma PCR was negative. CSF Mycobacterium tuberculosis culture was negative. JC virus antibodies in the blood and CSF were 1/81,920 and 1/20,489, respectively. The antibody index was 28, indicating intrathecal production of JC virus antibodies, which was consistent with progressive multifocal leukoencephalopathy (PML). Nested PCR for JC virus was positive in the CSF.