Fixed indirect immunofluorescence tests were done on imprints of 8 osteosarcomas and cells of tissue cultures derived from 5 osteosarcomas, with the use of sera from patients with this disease, from their family members, and normal blood-bank donors. Sera of 50% of patients and 30% of their family members contained antibodies to osteosarcoma cells. Sera of patients and their family members also reacted with cells of tissue cultures derived from 2 giant cell tumors, 2 rhabdomyosarcomas, and 1 chondrosarcoma, which suggested the presence of a common antigen in the tumors. Sera from normal donors gave negative reaction when tested against cells of the same tumors. The nature of the antigen demonstrated in cells of the tumors remains to be determined.