The binding of mouse B16-F10 melanoma cells to defined extracellular matrix components was studied using a dot-blot cell attachment assay. Radiolabeled melanoma cells adhered to immobilized elastin and laminin. Reduced binding was seen with fibronectin, collagen types I and IV, heparan sulfate, and bovine serum albumin. No adhesive activity was found in elastin associated microfibrillar proteins or in elastin fragments generated by alkali or acid digestion. Adherence to extracellular matrix components has been suggested to play a role in tumor spread to secondary sites. Our results indicate that elastin and laminin are the major extracellular molecules responsible for melanoma cell adhesion.