Mouse cell lines (L, NIH3T3, and RMA cells) infected with the Edmonston strain of measles virus (MV) did not exhibit cytopathic effects (CPE), consistent with the finding that mice are not susceptible to MV. Northern blot analysis, however, revealed that MV genes were transcribed in infected L and NIH3T3 cells, although expression levels were much lower than those in lytically infected Vero cells. Expression of MV genes was not detected in infected RMA cells. L and NIH3T3 cells were found to synthesize viral proteins and produce infectious virions after infection. These cell lines did not express on the surface the molecule detectable by antibodies directed against human CD46, the recently identified MV receptor. L cell transfectants expressing human CD46 exhibited CPE after MV infection, and produced 50 times more viral transcripts and 20 times more infectious virions than the parental L cells. The lowest titer of MV that induced viral multiplication in L cells as detected by cocultivation with Vero cells was larger than that in CD46+ L cells by two orders of magnitude. Our results indicate that MV can infect some mouse cells in the absence of CD46, yet the presence of CD46 facilitates multiplication and cytopathogenicity of MV in mouse cells.