The role of cellular adhesion in regional lymph node metastasis of solid tumors has been investigated. The data reviewed is based on studies in four different tumor models of human, rat and murine origin. An in vitro assay measuring tumor cell attachment to cryostat sections of normal peripheral lymph nodes, obtained from the species of tumor origin was used to compare the adhesion of tumor sublines with different metastatic potentials. A good correlation was found between tumor cell potential to metastasize to regional nodes and the adhesion to the sections in all models studied. The adhesion of all tumor lines could be blocked by Arg-Gly-Asp containing peptides while pretreatment of the cells with antibodies to integrins implicated beta 1 and beta 3 receptor complexes in the adhesion. Ligand binding assays provided indirect evidence that the preferential attachment of the metastatic tumor lines to the frozen sections was mediated via extracellular matrix proteins such as fibronectin, vitronectin and type IV collagen. As these basement membrane proteins have been localized to the outer surfaces of reticular fibers which are known to permeate the lymph node and trasverse the subcapsular sinus it is postulated that tumor cell attachment to these fibers may facilitate and possibly be required for tumor cell retention and growth in the invaded regional nodes.