Two sibling viruses, Fr/V and Fr/B, of the subacute sclerosing panencephalitis (SSPE) virus Osaka-2 strain were isolated from a small biopsy specimen of the brain of an SSPE patient by cocultivation with two different cell lines, Vero and B95a cells, respectively. These two sibling viruses differ from each other in their molecular mechanisms of defective M protein expression. In this study, we found that the Fr/B virus could scarcely form syncytium foci on Vero cells, although the Fr/V virus could do so on both Vero and B95a cells, showing a similar relation of cell tropism between recent field isolates and laboratory strains of the measles virus. Severe neurovirulence of both F/V and Fr/B viruses was observed in hamsters inoculated intracerebrally with less than 100 PFU, in contrast to the negative neurological and pathological findings in hamsters inoculated even with more than 101 PFU of their possible progenitor measles virus. Comparative sequence analysis of inoculated viruses and reisolated viruses from diseased hamster brains showed few variations at a region containing the P-NI gene junction, indicating that the inoculated viruses propagated in the brains and induced neurovirulence. All these results suggest that SSPE virus isolated with a lymphoid cell line is similar in neuropathogenicity to that isolated with a nonlymphoid cell lines, irrespective of differences in the molecular mechanism of M protein defectiveness.