Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a new protein that was isolated from bovine articular chondrocytes and human melanoma cell lines (melanoma inhibitory protein or MIA). In normal tissue its expression is limited to cartilage, and in morbid tissue to melanoma, chondrosarcoma, and breast cancer. Serum levels of CD-RAP/MIA correlate with the progression of malignant melanoma, but there have been no reports on chondrosarcoma. Here, it was first demonstrated by RT-PCR and immunohistological methods that CD-RAP was expressed in tissue from a Swarm rat chondrosarcoma that was used as an experimental model. The course following tumor transplantation and changes in serum CD-RAP after tumor excision were then observed to investigate whether serum CD-RAP could be used as a marker of tumor activity. Consequently, serum CD-RAP in control rats tended to decrease as the animal grew, whereas it rose in proportion to tumor proliferation in rats that had received a tumor graft. Serum CD-RAP levels dropped rapidly following excision of the tumor in a group of tumor-excised rats. In those rats which had a recurrence following excision of the tumor, serum CD-RAP rose prior to the appearance of the tumor. Serum CD-RAP thus sensitively reflected tumor onset and proliferation, so that it appeared to be an effective marker of tumor activity for Swarm rat chondrosarcoma.