Measles infection and the host immune response to measles virus was compared using naive and immunized rhesus monkeys. The monkeys were experimentally challenged with a wild-type strain of measles virus inoculated intranasally. After pathogenic virus challenge, measles virus was detected in mononuclear cells of peripheral blood, lymph node, and spleen in naive monkeys and viremia peaked on Day 7. However, only one of five vaccinated monkeys had a lower virus titer in peripheral blood mononuclear cells at one time point after challenge. No virus was detected in the lymphoid tissues from an immunized monkeys that was euthanized on Day 7 of infection. Measles-specific IgM, IgG, neutralizing antibody, and cytotoxic T lymphocytes were detected in vaccinated monkeys before challenge, but antibody titers were significantly lower in immunized monkeys than in naive monkey after challenge. Measles-specific IgG antibody and cytotoxic T cell responses were still detected more than 1 year after vaccination or infection. This animal model is useful for the further study of measles pathogenesis, immunosuppression, and immunologic memories.