A role for alpha beta and gamma delta T cells in protection against primary and secondary infection with Listeria monocytogenes was studied. The results show that mice depleted of either gamma delta T cells with 3A10 monoclonal antibody (mAb), or alpha beta T cells with anti-CD4 plus anti-CD8 mAb, or both types of T cells, remained capable of controlling Listeria multiplication during the first 4 days of primary sublethal infection. Moreover, mice depleted of either or both types of T cells also remained capable of resolving primary infection, although the absence of alpha beta T cells, but not gamma delta T cells, caused resolution to be slower. Likewise, Listeria-immune mice depleted of either alpha beta or gamma delta T cells remained capable of resolving secondary infection with a large inoculum of L. monocytogenes, although depletion of alpha beta T cells, and to a much lesser extent gamma delta T cells, resulted in early exacerbation of infection. However, immune mice depleted of both types of T cells lost their ability to resist a lethal Listeria challenge. Taken together, the results show that whereas neither type of T cell is needed for resistance to sublethal primary listeriosis, alpha beta T cells may act in concert with gamma delta T cells in protecting mice against lethal secondary infection. In addition, the results indicate that the role of gamma delta T cells in anti-listeria resistance is much less important than the role of alpha beta T cells, and can be demonstrated mainly in the absence of alpha beta T cells.