Small cell carcinoma of the lung is a highly lethal disease, killing nearly all patients afflicted with it. Although it metastasizes early and widely, it is exquisitely radiosensitive, and transient responses to this form of therapy are often dramatic. We have recently developed several monoclonal antibodies (MAb) reactive with antigens associated with this tumor. Scintigraphic and dual-label evaluations of their localization in nude mice bearing small cell carcinoma xenografts (derived from the human small cell carcinoma cell line NCI H69) were undertaken as a preliminary step in the eventual evaluation of their therapeutic potential. Anti-small cell MAb UM-MS1, 2, and 3, were labeled with 131I with the Iodobead method. Labeling efficiencies ranged from 68% to 88%. A control MAb, 225.28S (antimelanoma), was labeled with 125I by the same method. Although the labeled anti-small cell antibodies bound 20-40 times more to NCI H69 cells than did the antimelanoma control antibody, their total immunoreactive fraction was relatively low. Separate groups of nude mice bearing NCI H69-derived tumors were studied for imaging and localization with each 131I-labeled MAb. Successful imaging was achieved with two of the MAb; the quality of the images ranged from moderate to excellent. However, much of the localization to the tumors was due to nonspecific factors, as evidenced by the considerable tumor accretion of the control antibody.(ABSTRACT TRUNCATED AT 250 WORDS)