There is very limited evidence concerning the phenotype, function, and homing characteristics of memory T (T(M)) cells elicited by vaccination against intracellular bacteria in humans. Here we studied T(M) subsets elicited by exposure to Francisella tularensis in humans as a model of immunity to intracellular bacteria. To this end, T(M) cells were evaluated in two groups: (1) subjects immunized with live attenuated tularemia vaccine by skin scarification and (2) tularemia naturally infected subjects. In both groups the immune responses were mediated by CD4(+) and CD8(+) effector T(M) cells, mostly CD45RA(-)CD62L(-) and CD45RA(+)CD62L(-). Based on the expression of CD27, integrins alpha(4)/beta(7,) and alpha(4)/beta(1), it is likely that some of these T(M) cells have lytic potential and the ability to enter both mucosal and non-mucosal sites. Thus, regardless of whether by immunization or natural exposure, tularemia antigens elicited a broad spectrum of specific T(M) subsets with diverse homing characteristics.