A patient's immunologic response to a malignant tumor may be a major factor in determining his ultimate prognosis. An in vitro microcytotoxicity test using cultured tritiated thymidine (3HT) labeled osteosarcoma cells and autologous fibroblasts has been developed to determine the nature of this response. The role of cell mediated and serum factors has been quantitatively evaluated and the following results obtained. Osteosarcoma patients have been demonstrated to possess a normal cellular immune response which exhibits non-specific cytotoxicity in vitro. These patients can not differentiate their tumor cells from autologous fibroblasts, even though they may significantly suppress the growth of homologous tumors or fibroblasts. Serum blocking factors capable of inhibiting lymphocyte mediated cytotoxicity are occasionally noted. A reliable quantitative microcytotoxicity technique is presented which demonstrates that: (1) osteosarcoma is not due to host immuno-incompetence, (2) a common sarcoma antigen does not exist and (3) serum blocking factors may occasionally be present.