Sarcoma-specific cellular cytotoxicity was evaluated in patients with skeletal and softtissue sarcomas. Peripheral blood lymphocytes from 14 of 18 sarcoma patients were cytotoxic to an allogeneic osteosarcoma cell line, but not to fibroblasts from the same patient. Lymphocytes from patients after pelvic exenteration, who had received multiple blood transfusions, and lymphocytes from melanoma patients were nonreactive. Cellular immunity to osteosarcoma cells was demonstrated in patients with many histologic types of skeletal and soft-tissue sarcomas. The data support the concept of host transplantation resistance to a common human sarcoma antigen.