Abstract LFA-1 (CD11a/CD18) plays a key role in various inflammatory responses. Here we show that the acquired immune response to Listeria monocytogenes is highly biased toward type 1 in the absence of LFA-1. At the early stage of listeriosis, numbers of IFN-γ producers in the liver and spleen of LFA-1−/− mice were markedly increased compared with heterozygous littermates and Vα14+NKT cell-deficient mice, and NK cells were major IFN-γ producers. Numbers of IL-12 producers were also markedly elevated in LFA-1−/− mice compared with heterozygous littermates, and endogenous IL-12 neutralization impaired IFN-γ production by NK cells. Granulocyte depletion diminished numbers of IL-12 producers and IFN-γ-secreting NK cells in the liver of LFA-1−/− mice. Granulocytes from the liver of L. monocytogenes-infected LFA-1−/− mice were potent IL-12 producers. Thus, in the absence of LFA-1, granulocytes are a major source of IL-12 at the early stage of listeriosis. We assume that highly biased type 1 immune responses in LFA-1−/− mice are caused by increased levels of IL-12 from granulocytes and that granulocytes play a major role in IFN-γ secretion by NK cells. In conclusion, LFA-1 regulates type 1 immune responses by controlling prompt infiltration of IL-12-producing granulocytes into sites of inflammation.