β₂ integrins are of critical importance for leukocyte extravasation through vascular endothelia and for T cell activation. To elucidate the role of β₂ integrins in T cell–mediated immune responses, allergic contact dermatitis (ACD), irritant dermatitis, and delayed-type hypersensitivity (DTH) were assessed in mice lacking the β₂ integrin subunit, CD18. ACD and DTH responses, but not edema formation, were severely suppressed in CD18^–/– mice. Extravasation of CD18^–/– T cells into eczematous skin lesions was greatly impaired, whereas migration of Langerhans cell precursors and dendritic cells was normal in CD18^–/– mice. CD18^–/–lymph nodes (LNs) contained an abnormal population of CD3^–CD44^high lymphocytes and showed evidence of widespread T cell activation. T cells from regional LNs of sensitized CD18^–/– mice proliferated in response to hapten challenge, and subcutaneous injection of sensitized syngeneic LN cells directly into ears of hapten-challenged naive recipients restored the defective ACD in CD18^–/– mice, suggesting that CD18 is not required for priming of naive T cells but is indispensable for T cell extravasation. Thus, a dysfunction of T cells, in addition to granulocytes, may contribute to the pathophysiology of leukocyte adhesion deficiency type I, which arises from mutations in the human CD18 gene.