Background: \- Progressive multifocal leukoencephalopathy (PML) is a severe viral infection of the brain. It is caused by JC virus. Many people have this virus in their bodies all their life, but it is usually kept in check by their immune system. If the immune system does not work right because of a disease or medication, the virus becomes active and can damage cells in the brain. Not much is known about PML or how it affects the immune system. Researchers want to study people with PML to better understand the natural history of the disease.

Objectives: \- To study the natural history of PML.

Eligibility: \- Individuals at least 2 years of age who have PML.

Design: * Participants will be screened with a physical exam, medical history, and imaging studies. * Participants will have several visits to the National Institutes of Health Clinical Center. There will be an initial visit, monthly visits for the next 6 months, a 12-month visit, and possible visits afterward. * At the initial visit, participants will give blood, urine, and spinal fluid samples. They will also have neurological tests and imaging studies of the brain. * For the next five visits, participants will give blood and urine samples. They will also have neurological tests and imaging studies of the brain. * The 6-month and 12-month visits will repeat the tests from the initial visit. * Other optional procedures include bone marrow samples and skin biopsies. Additional blood tests and imaging studies may be performed. * Treatment will not be provided as part of this study.