Abstract Progressive multifocal leukoencephalopathy (PML) is a fulminating opportunistic infection of the brain that occurs in approximately 4% of AIDS patients. The need to diagnose and treat PML is urgent in patients with HIV as the infections are synergistic [Vazeux R, Cumont M, Girard P, et al. Severe encephalitis resulting from co-infection with HIV and JC virus. Neurology 1990;40:944–8]. Brain biopsy was previously required for definitive diagnosis. With positive JCV PCR CSF results and MR findings characteristic of PML, brain biopsy can be avoided in many AIDS patients [Weber T, Turner RW, Frye B, et al. Specific diagnosis of progressive multifocal leukoencephalopathy by polymerase chain reaction. J Infect Dis 1994;169:1138–41; Moret H, Guichad M, Matherson S, et al. Virological diagnosis of progressive multifocal leukoencephalopathy: detection of JC virus DNA in cerebrospinal fluid and brain tissue of AIDS patients. J Clin Microbiol 1993;10:3313; Post MJD, Yiannoutsos C, Simpson D, et al. Progressive multifocal leukoencephalopathy in AIDS: are there any MR findings useful to patient management and predictive of patient survival? AJNR Am J Neuroradiol 1989;20:1896–906]. A case is presented here and an overview of relevant literature is given.