Reactivation of latent JC virus in immunodeficient subjects can lead to a demyelinating disease following lytic oligodendrocyte infection. It is known as idiopathic CD4+ lymphocytopenia and rarely occurs in immunosuppressed patients who are not infected by HIV. We describe a case of persistent idiopathic CD4+ lymphocytopenia in an HIV-negative 65-year-old woman. At autopsy, polymerase chain reaction analysis evidenced JC virus DNA in kidney, brain and liver although there were no signs of progressive multifocal leukoencephalopathy or evidence of oligodendrocyte infection. While her disease was not HIV-induced, it closely resembled AIDS in terms of the nature of the immune derangement and the clinical picture. The case also evidences the reactivation of JC virus infection in non-HIV-related immunosuppression in cerebral and/or extracerebral sites: liver infection seems to be particularly relevant since it has not yet been recognized as a common target of JC virus infection or a source of virus spreading. The absence of any sign of progressive multifocal leukoencephalopathy was remarkable: histological examination failed to disclose demyelination or other progressive multifocal leukoencephalopathy changes, and the search for JC virus DNA with in situ methods also gave negative results. The lack of lytic brain infection in this case would seem to support the hypothesis that the expression of progressive multifocal leukoencephalopathy is directly dependent on the presence of HIV infection.