Binding of antigen-presenting cells (APC) to T cells via adhesion molecules is thought to deliver accessory signals that are required for efficient T-cell activation. To determine whether Langerhans cells (LC) express relevant adhesion molecules on their surfaces, we employed two-color immunofluorescence. Human epidermal cells (EC), Ficoll-enriched for LC (greater than 10%), were incubated with monoclonal antibodies (MoAb) specific for the adhesion molecules CD11a (LFA-1 alpha), CD18 (LFA-1 beta), or ICAM-1; staining was evaluated by fluorescence microscopy. After 12 h of culture only HLA-DR+ cells (LC) expressed CD11a, CD18, and ICAM-1. As a test for the functional relevance of such adhesion molecule expression, we examined the capacity of the above MoAb to block LC stimulation of alloreactive T cells: EC were co-cultured with allogeneic peripheral blood mononuclear leukocytes (PBML) for 5 d in the presence or absence of MoAb; proliferation was measured by [3H]-thymidine uptake. MoAb against CD11a, CD18, or ICAM-1 reduced the allostimulatory capacity of LC by greater than 70%; combinations of these MoAb reduced proliferation even more (90%). We conclude that interaction of adhesion molecules on LC with ligands on T cells is required for optimal allo-antigen-dependent T-cell activation, perhaps by delivering accessory signals.