ICAM-1 (CD54) plays an important role in the cell-cell interaction and migration of leukocytes. Previous studies have shown that ICAM-1 is involved in inflammatory reactions and that a defect in ICAM-1 gene inhibits allergic contact hypersensitivity. This study indicates that the migration of hapten presenting Langerhans cells into the regional lymph nodes was significantly reduced in ICAM-1-deficient mice compared to wild-type C57BL/6 mice. The reduced number of dendritic cells in regional lymph nodes did not result from abnormal migration of Langerhans cells into the skin of ICAM-1-deficient mice. The concentration and distribution of Langerhans cells in the naive skin of ICAM-1-deficient mice was equal to that of wild-type mice. Following hapten sensitization, Langerhans cell migration out of the skin and recruitment of fresh Langerhans cells back to the epidermis was not affected in ICAM-1-deficient mice. Further experiments demonstrated that ICAM-1 deficiency on lymphatic endothelium rather than on dendritic cells was responsible for the reduced migration of Langerhans cells into draining lymph nodes. This study indicates that ICAM-1 regulates the migration of dendritic cells into regional lymph nodes but not into or out of the skin.