Effector T cells control intracellular infection by secreting cytokines and through contact-dependent cytolysis. Because cytokines can diffuse and act at a distance, we determined whether cytokine diffusion is sufficient to control Mycobacterium tuberculosis or whether direct recognition of infected cells by CD4 T cells is required. Using MHC class II (MHC II) mixed bone marrow chimeras, we compared the bacterial burdens in lung myeloid cells that were capable (MHC II+/+) or not (MHC II−/−) of being recognized by CD4 T cells. MHC II+/+ cells had lower bacterial burdens than did MHC II−/− cells. CD4 T cell depletion increased the number of bacteria associated with MHC II+/+ cells but not MHC II−/− cells, indicating that direct recognition of infected cells by CD4 T cells is required for control of intracellular M. tuberculosis. These results show that the effector mechanisms required for CD4 T cell control of distinct intracellular pathogens differ and that long-range cytokine diffusion does not contribute to control of M. tuberculosis.