The serologic cross-relationship between three new human papovaviruses and SV40, polyoma virus and wart virus, were studied by immune electron microscopy. The human papovaviruses were; JC virus and SV40-PML virus isolated from human brains with the demyelinating disease progressive multifocal leukoencephalopathy (PML), and BK virus isolated from the urine of a renal transplant patient without PML. Antisera to these viruses were prepared in rabbits and the antibody-antigen complexes formed after incubation of viruses with antisera were examined in the electron microscope. Antibody molecules were seen as filaments projecting from the capsid of the virions. When using a 1:10 serum dilution, two-way cross-reactions occurred between BK virus with JC antiserum and JC virus with BK antiserum; and also between SV40-PML virus with SV40 antiserum and SV40 with SV40 antiserum. One-way crosses were seen between JC virus and SV40-PML antiserum, SV40-PML virus and BK antiserum, and SV40 virus and JC antiserum. The possible significance of these results is discussed.