Sera from eleven patients bearing osteogenic sarcomas were tested for reactivity against autologous and allogeneic normal and tumor cells using a sensitive microcytotoxicity assay. Following absorption with human fetal tissue cultured lines, sera from all 11 patients lost reactivity to autologous and allogeneic normal fibroblasts in culture. However, sera from four patients retained reactivity against both autologous and allogeneic osteogenic sarcoma, sera from five patients retained reactivity to allogeneic but not autologous tumor, and sera from two patients lost all reactivity to tumor. Sera from nine normal individuals did not react with either normal or osteogenic sarcoma cells after fetal cell absorption. Thus it appears that nine of 11 patients bearing osteogenic sarcoma contained antibody to a common tumor-associated antigen. This tumor-associated antigen appears to be expressed on tumor cells and not normal cultured cells, and reactivity to it is present in tumor-bearing but not normal individuals.