The role of extracellular matrix (ECM) proteins in supporting tissue structure and modulating cell moltility or phagocytosis is well established. Recent demonstration of complex in vitro interactions between lymphocytes and ECM components mediated by an array of cell surface adhesion receptors supports the role ECM may play in physiological functioning of the immune system in vivo, e.g. cell activation, migration and positioning in specific tissue microenvironments. Thus, ECM components and their lymphocyte adhesion ligands should be considered as active participants in the host immune responses, including that triggered by transplantation of an MHC-incompatible organ graft.