Monoclonal antibodies to small cell lung cancer (SCLC) were produced by fusion of P3X63/AgU1 mouse myeloma cells with spleen cells from BALB/cmice immunized against intact cells of SCLCtumors grownin BALB/c athymic nude mice. The antibody TFS-2 demonstrated "pancarcinoma"reactivity showing binding to non-small cell lung cancer (NSCLC)and carcinomas derived from other organs such as stomach, pancreas, and colon. This antibody failed to react with a variety of normal tissues including lung, bone marrow, spleen, stomach, colon, and pancreas. TFS-2 showed complement-mediated cytolysis of target cells. TFS-2 had no significant effects on hematopoietic stem cells. This antibody will serve as a powerful tool for the in vitro removal of tumor cells from bone marrow, thus facilitating highdose chemotherapy of SCLCwith autologous bone marrow transplantation. In contrast, TFS-4 monoclonal antibody reacted specifically with SCLCbut not with NSCLStumors. This antibody can distinguish SCLCfrom NSCLCtumors in histologic diagnosis at transbronchial biopsy, and in cytological identification of tumor cells in malignant effusion, and in infiltrated bone marrow. Radiolabeled TSF-4 specifically accumulated into SCLCtumors that were implanted subcutaneously into athymic nude mice. Thus, the antibody will be useful not only for diagnosis of lung cancer but also for targeting anti-tumor agents.