The innate immune response to viral infections often includes induction of types I and III interferons (IFNs) and production of antiviral proteins. Measles is a severe virus-induced rash disease, but in vitro studies suggest that in the absence of defective interfering RNAs, neither wild-type (WT) nor vaccine strains of measles virus (MeV) induce IFN. To determine whether IFN is produced in vivo, we studied tissues from macaques infected with vaccine or WT strains of MeV using quantitative reverse transcriptase-polymerase chain reaction to assess levels of IFN and IFN-stimulated gene (ISG) mRNAs and a flow cytometry-based bioassay to assess levels of biologically active IFN. There was little to no induction of type I IFN, type III IFN, Mx, or ISG56 mRNAs in monkeys infected with vaccine or WT MeV and no IFN detection by bioassay. Therefore, the innate responses to infection with vaccine or WT strains of MeV are not dependent on IFN production.