INTRODUCTION Osteosarcoma (OS) is the most common primary malignancy of bone. One-third of OS patients succumb to overwhelming pulmonary metastatic disease that is refractory to chemotherapy and surgery. Recent research suggests that bone morphogenetic protein (BMP) expression correlates positively with the incidence of OS pulmonary metastases and negatively with disease-free survival. Other reports indicate that OS patients with high serum vascular endothelial growth factor (VEGF) concentrations are more likely to develop metastases. K7M2 and K12 are related cell lines derived from a spontaneously occurring OS in a Balb-C laboratory mouse. K7M2 displays aggressive metastatic potential in vivo, whereas K12 is much less metastatic. The current study was designed to test two hypotheses: (1) OS cell lines with differing metastatic potentials have different BMP and VEGF expression patterns and (2) A BMP antagonist, Noggin, will alter OS cell growth in vitro.