AbstractAlkaline phosphatase (AP) activity and expression of bone Gla protein (BGP), c‐fos, and c‐jun were compared in two transplantable osteosarcomas with high potentials for metastasis to the lung. The original spontaneous osteosarcoma (SOS) gradually became histologically undifferentiated, losing its osteogenic activity during serial transfer, whereas the chemical (4‐hydroxyaminoquinoline 1‐oxide)—induced osteosarcoma (COS) retained osteogenesis. The two osteosarcomas showed similar doubling times and levels of lung metastasis, and strong AP activity was detected on the cell membranes of both. Northern blot analysis revealed that lack of BGP mRNA expression was associated with expression of both c‐fos and c‐jun proto‐oncogenes in SOS. In contrast, neither c‐fos nor c‐jun mRNAs were detected but BGP mRNA was expressed in the case of COS. These results suggest that the c‐fos and c‐jun genes may suppress the expression of BGP mRNA relevant to differentiation and osteoid formation in rat osteosarcomas. However, this does not appear to be directly related to proliferative or metastatic biological behavior.