In the normal course of an immune response, both CD4+ and CD8+ T cells respond to each of the bacterial pathogens we have discussed and both responses may be required for the most potent immunity to infection. In this discussion, we have focused on the ability of these organisms to prime CD8+ T-cell responses in vivo and the ability of CD8+ T cells as sole mediators of acquired immunity, to protect against infection. It is clear that the vacuolar location of bacterial pathogens such as Salmonella or Mycobacteria does not prevent in vivo priming of CD8+ T-cell responses to these pathogens. However, vacuolar localization may affect the potency of CD8+ T-cell responses under experimental conditions that assess the capacity of CD8+ T cells as the sole mediators of acquired immunity. In the case of cytoplasmic L. monocytogenes, clear evidence exists that antigen-specific CD8+ T cells, in the absence of immune CD4+ T cells, can provide substantial acquired immunity to naive mice. Similar clear experimental results with Salmonella and Mycobacteria are lacking. Such results would provide stronger support for vaccines that elicit CD8+ T-cell responses to these vacuolar pathogens. Although our discussion has focused on only three specific organisms, we suggest that detection of an in vivo CD8+ T-cell response to a bacterial antigen does not ensure that the response will be protective against infection in a vaccine setting. In the case of Salmonella and Mycobacteria, this issue remains unresolved.