An indirect, isotope-labeled antibody technique was developed to demonstrate antigen-antibody interactions in vitro with cells that do not ordinarily undergo a cytotoxic reaction. With125I-labeled goat anti-mouse immunoglobulin, it was possible to demonstrate absorption of mouse antibodies directed against normal H-2 antigens on the surface of normal lymphoid cells, sarcoma cells growing in the ascites form, and sarcoma cells prepared from trypsinized portions of solid tumor. Tumor-specific antigens were demonstrated on cells of a Friend virus-induced lymphoma and a methylcholanthrene-induced sarcoma. In the latter instance, mice with transplants of the tumors from isologous mice had significant levels of circulating antibody only after the immunizing tumor was excised.