Macrophages (Mø) and dendritic cells (DC) are thought to be targets of measles virus (MeV) at the early stage of infection. We compared the growth of Edmonston-derived vaccine strains and fresh clinical isolates of MeV in monocytes, monocyte-derived granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced Mø (GM-Mø) and in monocyte-derived DC (Mo-DC). Neither vaccine strains nor fresh isolates thrived in monocytes and GM-Mø and no differences were evident among them. On the other hand, infectious virus production was robust in Mo-DC infected with fresh isolates, but below the limits of detection in those infected with vaccine strains. Although the vaccine strains infected Mo-DC and replicated comparably with the fresh isolates, they accumulated far less matrix (M) protein. This was attributed to a difference in the stability of M protein produced in Mo-DC between the strains. Impaired production of infectious viruses in DC may be one cause of vaccine strain attenuation.