Recent investigations have indicated a role for antigen-specific T lymphocytes in the local skin immunity. The cutaneous lymphocyte antigen (CLA) is supposed to represent a skin-homing receptor for T cells. Inhibition experiments with specific monoclonal antibody demonstrate that CLA participates in selective transendothelial migration of memory/effector T cells in vitro by interaction with E-selectin on endothelial cell layers after activation with proinflammatory cytokines. In addition, the receptor-ligand pairs VLA-4/VCAM-1 and LFA-1/ICAM-1 are involved in this process. Moreover, only CLA+, CD45RO+ (memory/effector) T cells freshly isolated from peripheral blood of patients with allergic contact dermatitis or atopic dermatitis specifically proliferate in response to the respective allergen. CLA-, CD45RO- T cells from these patients do not respond to the allergens. In contrast, memory T cells from asthmatic individuals and patients with both asthma and atopic dermatitis express the allergen specificity in both T cell subsets. Tetanus toxoid, a systemically acting antigen, also induces a proliferative response in both CLA+ and CLA- memory/effector T cell subsets. These results strongly support the selective role of CLA in homing T cells to the cutaneous tissues and therefore playing a role in the local immunity and inflammatory reactions of the skin.