Indirect immunofluorescence and flow cytometry were used to determine reactivity of a panel of 75 monoclonal antibodies (MAbs) and controls (provided by the Third International IASLC Workshop on Lung Tumor and Differentiation Antigens) with 3 morphologically similar prototype continuous-culture small-cell-carcinoma cell lines (SCC) (NCI-H69, NCI-H146, and NCI-H510). All cell lines had some reactivity with some of the MAbs. There is, however, differential expression of antigens amongst the prototype cell lines, which may provide a useful method for phenotyping and sub-classifying SCC. The reactivity of the 3 cell lines was greatest with MAbs in Clusters I, 1c, 2, 4, 6, and 9, and least with MAbs in clusters W7, 8, 13, 14, and W15, with few exceptions. Although morphologically similar, each of the SCC cell lines has a unique pattern of reactivity with the workshop MAbs. For example, although a control MAb, CD56 (NKHI), which identifies an epitope on NCAM (neural cell adhesion molecule) common among many SCC lines, stained more than 90% of cells in each of the prototype cell lines, one MAb of the current panel, SEN7, which also identifies a CD56 epitope on 15 SCC lines did not react as strongly with H-146 and H-510 as with H-69. If appropriately reactive MAbs can be identified for individual patients' tumors, they can be coupled to suitable radioisotopes or toxins for individualized patient treatment.