Interactions between tumor cells and laminin or other components of the extracellular matrix are thought to play a role in tumor invasion and metastasis. To analyze these interactions, we examined the expression of 5 types of laminin receptors on 11 cell lines derived from the highly malignant and metastatic tumor small-cell lung cancer (SCLC). The integrins VLA-1, VLA-3, VLA-6 and the 67 KDa monomeric receptor were expressed at various levels, whereas the VLA-2 receptor was absent on the cell lines. Only one cell line expressed none of these laminin receptors. All cell lines co-expressed alpha 6 beta 1 (VLA-6) and the 67-kDa molecule, the only receptors specific for laminin. Analysis of the ability of SCLC cells to bind radiolabeled laminin and to adhere to laminin substrata revealed a correlation between these 2 parameters and the expression of VLA-6 and the 67-kDa monomeric receptor. Cell adhesion was mediated by alpha 6 beta 1, as indicated by inhibition of adhesion using an anti-VLA-6 monoclonal antibody (MAb). Both VLA-6 and the monomeric receptor were up-regulated in vitro by laminin.