To understand the interaction between hepatocyte growth factor (HGF) and its receptor c-Met on various bone and soft tissue tumors, their expressions were investigated by western blot analysts, immunohistochemistry and enzyme immunoassay. Western blot analysis revealed that c-Met protein was expressed in 21 (38.8%) of 54 tumors, which detailed to seven (25.9%) of 27 bone tumors and 14 (51.8%) of 27 soft tissue tumors. Most malignant fibrous histiocy-tomas (MFH) and all neurofibromas expressed c-Met protein. The highest expression of c-Met protein was seen in a case of biphasic synovial sarcoma, where its immunoreac-tivity was localized only on the epithelial component and not on the sarcomatous component. By enzyme immunoassay for HGF, all but one MFH showed HGF production and the mean level of HGF was the highest among the tumors investigated. Neurofibmmas and osteosarcomas had the next highest mean levels of HGF production, respectively. Coexpression of HGF and c-Met was obsewed in 19 (35.2%) of 54 tumors and was frequently observed in neurofibroma, followed by MFH and synovial sarcoma. Although the mode of interaction between HGF and c-Met varies among the various bone and soft tissue tumors including MFH, their signaling system may play an Important role in the development and progression of bone and soft tissue tumors.