Although it is well established that CD4⁺ T cells are required for the protective immune response against tuberculosis (TB), there is some evidence that CD8⁺ T cells are also involved in the host response to Mycobacterium tuberculosis. There is, however, a paucity of information on the pulmonary CD8⁺ T-cell response during infection. We therefore have compared the changes in both CD8⁺ and CD4⁺ T cells following aerosol infection withM. tuberculosis. There was an observed delay between the peak of infection and the activated T-cell response in the lung. The kinetics of CD8⁺ and CD4⁺ T-cell responses in the lung were identical, both peaking at week 8, 4 weeks later than the peak of cellular response in draining lymph nodes. Similar changes in activation/memory phenotypes occurred on the pulmonary CD8⁺ and CD4⁺ T cells. Following in vitro restimulation, both subsets synthesized gamma interferon, a cytokine essential for controlling M. tuberculosis infection. Since lung CD8⁺ T cells are actively expanded during aerosolM. tuberculosis infection, it is important that both CD8⁺ and CD4⁺ T cells be targeted in the design of future TB vaccines.