The growth of respiratory syncytial (RS) virus in primary mouse embryo (ME) cells was investigated. The virus yields in ME cells were markedly lower if compared with those in HEp-2 cells, which are fully permissive for RS virus, and a remarkable production of interferon (IFN) was found in the early period of infection of the former cells. The virus yields in ME cells were enhanced when antimouse IFN serum was added to the medium. Indirect immunofluorescent staining of infected ME cells showed that the infection spread in the entire monolayer in the presence of antiserum, whereas it was markedly restricted throughout in the absence of the serum. All the major viral polypeptides were synthesized in the absence of the serum. However, their synthesis rates were greatly enhanced if the antiserum was added. These results suggest that the virus growth in ME cells is self-limiting and that this limited growth is due to autointerference by endogenously produced IFN during the course of infection. Further, this type of growth restriction of RS virus appears to be characteristic of cells of mouse origin by comparative studies that used other cells of different origin.