Sera from osteosarcoma patients were used in an indirect immunofluorescence assay to detect sarcoma‐specific antigen(s) in human osterosarcomas. Fifty‐seven of 58 of these sera and two of 24 normal sera reacted with osteosarcoma tissue as demonstrated by the fluorescence of both cell membrane and cytoplasm. Human osteosarcoma sera also detected sarcoma‐specific antigen(s) in six of seven sarcomas induced in hamsters inoculated at birth with cell‐free extracts of human osteosarcomas. Hamster carcinomas, reticular tissue tumors, and normal tissues failed to react with human osteosarcoma sera. The presence of human sarcoma‐specific antigen(s) in the sarcomas of six hamsters treated with human osteosarcoma extracts suggests that these tumors were induced by a human osteosarcoma virus.