The efficiency of prime-boost vaccinations on the induction of T-cell responses to Sin Nombre virus nucleocapsid protein expressed by recombinant vaccinia virus, replication-deficient adenovirus, and plasmid DNA in mice was quantitated by the number of epitope-specific interferon-gamma-producing T cells and cytotoxic T-lymphocyte activity induced. In prime-boost immunizations, all combinations that included the recombinant adenovirus induced a much higher number of epitope-specific interferon-gamma-producing T cells than did other combinations. A single immunization of the recombinant adenovirus was able to induce similarly high levels of epitope-specific interferon-gamma-producing cells, despite the fact that the recombinant adenovirus produces less amount of the Sin Nombre virus nucleocapsid protein.