Human monoclonal antibodies were isolated from stomach carcinoma patients by the fusion of spleen and lymph node lymphocytes with the heteromyeloma line SPM4-0. Initial screening was carried out on autologous primary tumor cell cultures in an adhesion assay in order to select surface-reactive functional antibodies. This was followed by live cell immunoperoxidase staining assays. The human monoclonal antibody SC-1 was found to selectively react with cultured cells isolated from autologous and allogeneic stomach carcinoma patients, and with cryostat sections of the primary tumors. More extensive screening revealed that the antibody showed no reactivity with a wide range of tumor tissues and normal cells. Some reactivity was present on fetal tissues. SC-1 inhibits movement of the autologous tumor cells and identifies a protein with a molecular weight of 50,000. This study demonstrates that, with the use of selective screening assays on primary tumor material, it is possible to isolate antibodies which not only result from an immune response in the patient but also interfere with intercellular processes of tumor cells.