The β₂ integrins are important for transendothelial migration of leukocytes as well as for T-cell activation during antigen presentation. Despite abundant expression of β₂ integrins on antigen-presenting cells (APCs), their functional relevance for antigen presentation is completely unclear. We show here that dendritic cells (DCs) from CD18-deficient mice, which lack all functional β₂ integrins, have no defect in antigen presentation. Moreover, DCs from normal mice express inactive β₂ integrins that do not become activated on contact with T cells, at least in vitro. Pharmacologic activation of β₂ integrins on DCs results in a significant reduction of their T cell–activating capacity. This effect is mediated by Mac-1 (CD11b/CD18) on DCs because it could be reversed via blocking antibodies against CD18 and CD11b. Furthermore, the antigen-presenting capacity of macrophages, which express constitutively active β₂ integrins, is significantly enhanced on Mac-1 blockade. We therefore conclude that active CD11b/CD18 (Mac-1) on APCs directly inhibits T-cell activation.