The T-box transcription factor T-bet is an important regulator of IFN-gamma production in all cell types and is considered to be essential for the generation of CD4 Th1 T cells. IFN-gamma in turn plays a critical role in immunity to many infectious agents. In this study, we demonstrate that T-bet is not required for host resistance to primary Listeria monocytogenes (LM) infection. In the innate immune phase, control of LM replication, serum IFN-gamma, and numbers of IFN-gamma-producing NK cells were similar in T-bet-deficient and control mice. In the adaptive immune phase, there was no defect in bacterial clearance or in the numbers of LM-specific IFN-gamma-producing CD8 T cells in T-bet-deficient mice and only a modest, although significant, reduction in the numbers of Th1 CD4 T cells and IFN-gamma secretion by CD4 T cells. Thus, host resistance and the generation of IFN-gamma-producing cells in response to LM infection are not substantially compromised in the absence of T-bet.