Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease characterized by infection of oligodendrocytes by JC virus. The exact nature of the pathogenesis of PML is not known. The nature of the primary infection, the site of viral latency, and the route by which JCV enters the brain remain to be elucidated. Different laboratories have shown the presence of JCV in peripheral lymphocytes from immunosuppressed individuals, suggesting these cells as possible carriers of JCV to the brain. To examine this observation, we tested the susceptibility to JCV infection of cells from lymphoid organs, focusing our attention on CD34+ haematopoietic precursor cells and B lymphocytes. The results demonstrate that both these cell types are susceptible to JCV infection and, moreover, that JCV can infect only those cells that differentiate into lymphocytic lineage.