Dendritic cells (DC) form a distinct hemopoietic lineage of specialist antigen-presenting cells (APC) with unique abilities to stimulate a primary T lymphocyte response in vitro. In vivo data indicate that the interstitial DC in allografted tissue likewise stimulate an allogeneic response. DC express a range of adhesion molecules which are relevant to their interaction with T lymphocytes including ICAM-1, a ligand for T lymphocyte LFA-1. The T lymphocyte LFA-1 interaction with its DC ligand(s) plays a major role in DC-mediated activation of allogeneic T lymphocytes. This study details the expression of ICAM-1 and ICAM-2, a ligand for LFA-1, on cells of the DC lineage and examines their contribution to the DC-stimulated MLR response. Sensitive immunofluorescence and immunoperoxidase studies using newly available anti-ICAM-2 reagents failed to detect ICAM-2 or ICAM-1 on skin Langerhans cells, liver, and kidney interstitial DC. Isolated blood and tonsil DC were ICAM-1 and weakly ICAM-2 positive. Functional studies with CBR-IC2/2, an antibody known to block ICAM-2 binding to LFA-1, did not have a significant inhibitory effect on the DC-stimulated allogeneic MLR. Likewise we were again unable to show a major role for ICAM-1 in these DC-T cell interactions. These results suggest that other DC ligands for LFA-1, perhaps ICAM-3, may be present on DC and act as the major functional ligand for T cell activation.