We reported previously that IL-15 plays a critical role in protecting effector CD8(+) T cells from apoptosis during the contraction phase following acute infection with Listeria monocytogenes by inducing antiapoptotic molecules. In the present study, we examined the effects of in vivo administration of rIL-15 on contraction of CD8(+) T cells after chronic infection with Mycobacterium bovis BCG and on the efficacy of BCG vaccination against Mycobacterium tuberculosis infection. Antigen-specific CD8(+) T cells reached an expansion peak at approximately Day 21, followed by a contraction after inoculation with rBCG expressing OVA. In vivo administration of rIL-15 from Days 22 to 42 after BCG inoculation inhibited apoptosis of effector CD8(+) T cells by up-regulating their Bcl-2 expression, resulting in a significant increase of antigen-specific memory CD8(+) T cells producing IFN-gamma. However, the IL-15 treatment did not elicit improved efficacy of BCG vaccination against M. tuberculosis. These results suggest that IL-15 plays a critical role in protecting activated CD8(+) T cells from apoptosis during the contraction phase following BCG inoculation, although IL-15 administration alone at the contraction phase might not be sufficient to protect the efficient memory T cell responses against subsequent infection with M. tuberculosis.