Measles virus causes a severe systemic illness. The rash occurs simultaneously with the onset of the effector phase of the antiviral immune response and substantial evidence of immune activation. This immune response is effective in clearing virus and in establishing long-term resistance to reinfection but is associated with immune suppression, autoimmune encephalomyelitis, and increased susceptibility to secondary infections. This apparent paradox may be explained in part by preferential long-term activation of type 2 CD4+ T cells by measles virus infection. Preferential stimulation of type 1 CD4+ T cells by inactivated virus vaccines is hypothesized to play a role in subsequent development of atypical measles.