BACKGROUND To develop a new immunologic approach to multiple myeloma, the authors generated a monoclonal antibody against a human plasma cell specific antigen, HM1.24. Their previous study showed the antitumor effect of this antibody in severe combined immunodeficiency (SCID) mice bearing human myeloma xenografts. In the current study, the efficacy of anti-HM1.24 immunoglobulin (Ig) G and its F(ab')2 fragment were evaluated for radioimmunologic detection of the myeloma xenografts. METHODS SCID mice bearing subcutaneous RPMI 8226 tumors were injected with 125I-labeled antibodies, and radioactivity in the tumor and normal tissues was measured. Radioimmunoscintigraphy and autoradiography were performed to investigate the distribution of the antibodies. RESULTS In comparative biodistribution studies, the maximum tumor localization index of anti-HMl.24 F(ab')2 fragment was significantly higher than that of anti-HM1.24 IgG. Anti-HM1.24 F(ab')2 consistently had higher tumor-to-tissue ratio than anti-HM1.24 IgG and gave distinct tumor images by radioimmunoscintigraphy. Autoradiographic study showed that anti-HM1.24 F(ab')2 penetrated the tumor mass more uniformly than whole IgG antibody. CONCLUSIONS These results indicate that anti-HM1.24 antibody has the potential to provide a new approach to the immunodetection and immunotherapy of multiple myeloma and related plasma cell dyscrasias.