Bone morphogenetic proteins, which are capable of inducing mesenchymal tissue to form bone in mammals, have been implicated as important in normal skeletal development. The expression of bone morphogenetic proteins and their receptors were studied in 36 osteosarcoma specimens, six Ewing's sarcomas, 20 synovial sarcomas, and 20 chondrosarcomas by reverse transcriptase-polymerase chain reaction, and the findings were correlated with clinical data. Bone morphogenetic protein-2, and -4 messages were detected in most sarcoma samples. Bone morphogenetic protein-6 expression was detected in 22 of 32 osteosarcomas and seven of eight chondrosarcomas. Bone morphogenetic protein-7 and receptor IB were not detected in sarcoma samples but were detected in three osteosarcoma cell lines and one malignant fibrous histiocytoma cell line. Expression of bone morphogenetic protein receptor II was found in 25 of 36 osteosarcomas, eight of 20 chondrosarcomas, four of six Ewing's sarcomas, and 15 of 20 synovial sarcoma samples. Expression of bone morphogenetic protein type II receptor was found to correlate with metastasis in osteosarcomas, which suggests that the bone morphogenetic protein pathway may participate in tumor aggressiveness or progression. The expression of bone morphogenetic protein receptor II in metastatic synovial sarcoma and dedifferentiated chondrosarcoma lesions also supports this hypothesis. The current study showed that the ligands for bone morphogenetic protein receptors, bone morphogenetic proteins-2, -4, and -6 also are expressed in osteosarcoma and other sarcoma tissues, indicating a potential for autocrine or paracrine growth stimulation in these tumors.