Cells of the melanocytic lineage have been shown to be capable of producing laminin and to lose this property during transformation. In the present study, we have evaluated immunohistochemically whether these changes are paralleled by an altered expression of the alpha 6/beta 1 laminin receptor. Results of this analysis have shown that while nevic cells display high levels of the receptor, this heterodimer undergoes a progressive decrease in expression in cutaneous melanomas of increasing invasiveness. A loss or unco-ordinated expression of the alpha 1/beta complex is present in the majority of the metastatic foci at different body sites. The present results show that during transformation the alpha 6/beta 1 laminin receptor undergoes quantitative alterations and deregulated expression of the 2 subunits. Although the functional relevance of these changes remains unknown, their occurrence in association with modifications of other cellular and extracellular macromolecules associated with tumor progression, strongly suggests a role in human melanoma progression.