In order to investigate whether a B-cell immune response to the polymorphic epithelial mucin (PEM) is present in adenocarcinomatous patients, peripheral blood lymphocytes from 20 patients with adenocarcinomas from various sites were fused with the mouse-human heteromyeloma cell line SHM-D33. One IgM(K) monoclonal antibody derived from peripheral blood lymphocytes of a patient with a lung adenocarcinoma was generated with binding reactivity for bovine submaxillary mucin (BSM). The latter is one of the PEMs, and it contains a large amount of the tumor-associated sialosyl-Tn epitope. The generated antibody was designated KMD-2. Immunohistological studies on various tissues showed that KMD-2 reacted with 6/6 colorectal adenocarcinomas and 4/6 pulmonary adenocarcinomas. The antibody also displayed a slight degree of cross-reactivity with a limited number of normal tissues, especially those that elaborate mucin. Our data show that an autologous antibody response in the form of IgM to the immunosuppressive PEM is present in some adenocarcinomatous patients. The data also suggest that the KMD-2 (IgM/K) antibody may be of clinical importance for diagnostic purposes of adenocarcinomatous disease.