Polyclonal antibodies were raised against mouse multinucleated giant cells to identify proteins specifically associated with multinucleated macrophages. A 115 kd membrane protein and a 160 kd soluble protein were detected by immunoprecipitation of radiolabeled giant cells and were not seen in mononucleated macrophages. This study demonstrated that giant cells express de novo synthesized proteins that are not present in macrophages and identified a new immunization technique to generate antibodies directed against cell surface components.