We studied the expression of the members of the beta 1 integrin family and extracellular matrix ligands in osteosarcoma tissues. Immunostaining of primary osteosarcomas with use of specific antibodies for alpha 1-alpha 6 integrin subunits, fibronectin, type-I collagen, and laminin gave characteristic patterns: despite the diffuse expression of type-I collagen in all 16 osteosarcomas, collagen receptors were detected in only one. Laminin and laminin receptors were expressed poorly. In contrast, the alpha 4 and alpha 5 fibronectin receptors were found in 100 and 75%, respectively, which correlates very well with the strong expression of fibronectin in the stroma. The other ligand for alpha 4, vascular cell adhesion molecule-1, was not expressed in the seven specimens tested. Therefore, primary osteosarcomas closely interact with fibronectin through alpha 4 and possibly alpha 5 subunits of the beta 1 integrin. We also examined the expression of integrins in six metastatic foci in five patients. Some change for the expression was detected in all six specimens, however, the change varied. In contrast, osteosarcoma cells obtained from invasive portions of tumors exhibited new and augmented expression of certain integrins in two of the three cases in which their ligands were also expressed.