Lack of a vaccine for infants and immunosuppression after infection are problems associated with measles virus (MV). Because interleukin (IL)-12 has been used successfully as a vaccine adjuvant and because inhibition of IL-12 expression has been associated with immunosuppression during measles, the addition of IL-12 may enhance the immune response to MV. To determine the effect of IL-12 supplementation, rhesus macaques were vaccinated with a recombinant MV expressing IL-12; these macaques had increased interferon-gamma production by CD4(+) T cells, decreased production of IL-4, and lower levels of MV-specific immunoglobulin G4 and neutralizing antibody. Lymphoproliferative responses to mitogen were not improved. IL-12 supplementation altered the T helper type 2 bias of the immune response after MV vaccination, had a detrimental effect on the protective neutralizing antibody response, and did not improve other manifestations of immunosuppression. Reduced IL-12 levels are not the sole factor in MV-induced immunosuppression.